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4. A cost-consequence analysis of adding pertuzumab to the neoadjuvant combination therapy in HER2-positive high-risk early breast cancer in Italy

Author

Zambelli, A, Cazzaniga, M, La Verde, N, Munzone, E, Antonazzo, I, Mantovani, L, Di Cosimo, S, Mancuso, A, Generali, D, Cortesi, P, Zambelli A., Cazzaniga M., La Verde N., Munzone E., Antonazzo I. C., Mantovani L. G., Di Cosimo S., Mancuso A., Generali D., Cortesi P. A., Zambelli, A, Cazzaniga, M, La Verde, N, Munzone, E, Antonazzo, I, Mantovani, L, Di Cosimo, S, Mancuso, A, Generali, D, Cortesi, P, Zambelli A., Cazzaniga M., La Verde N., Munzone E., Antonazzo I. C., Mantovani L. G., Di Cosimo S., Mancuso A., Generali D., and Cortesi P. A.

Abstract

Introduction: Clinical trials confirmed the beneficial effects of adding pertuzumab (P) to the combination of trastuzumab-chemotherapy (TC) in the (neo)adjuvant setting of high-risk HER2-positive early breast cancer (HER2+BC). We evaluated the clinical, economic and societal impact of adding pertuzumab to neoadjuvant TC combination (TPC) in Italy. Methods: A cost-consequence analysis comparing TPC vs. TC was performed developing a cohort-based multi-state Markov model to estimate the clinical, societal and economic impact of the neoadjuvant therapy of TPC versus TC in HER2+BC at high-risk of recurrence. The model works on a cycle length of 1 month and 5-years-time horizon. Literature review-based data were used to populate the model. The following clinical and economic outcomes were estimated: cumulative incidence of loco-regional/distant recurrences, life of years and QALY and both direct and indirect costs (€). Finally, sensitivity analyses were performed. Results: TPC was associated with a 75,630 € saved of direct costs. Specifically, it was associated with an initial increase of treatment costs (+4.8%) followed by reduction of recurrence management cost (−20.4%). TPC was also associated with an indirect cost reduction of 1.40%, as well as decreased incidence of distant recurrence (−20.14%), days of work lost (−1.53%) and days lived with disability (−0.50%). Furthermore, TPC reported 10,47 QALY gained (+2.77%) compared to TC. The probability to achieve the pathological complete response (pCR) was the parameter that mostly affected the results in the sensitivity analysis. Conclusion: Our findings suggested that TPC combination could be a cost-saving option in patients with HER2+BC at high-risk of recurrence.

Published
2023

5. Adjuvant capecitabine in triple negative breast cancer patients with residual disease after neoadjuvant treatment: real-world evidence from CaRe, a multicentric, observational study

Author

Di Lisa, F, Krasniqi, E, Pizzuti, L, Barba, M, Cannita, K, De Giorgi, U, Borella, F, Foglietta, J, Cariello, A, Ferro, A, Picardo, E, Mitidieri, M, Sini, V, Stani, S, Tonini, G, Santini, D, La Verde, N, Gambaro, A, Grassadonia, A, Tinari, N, Garrone, O, Sarobba, G, Livi, L, Meattini, I, D'Auria, G, Vergati, M, Gamucci, T, Pistelli, M, Berardi, R, Risi, E, Giotta, F, Lorusso, V, Rinaldi, L, Artale, S, Cazzaniga, M, Zustovich, F, Cappuzzo, F, Landi, L, Torrisi, R, Scagnoli, S, Botticelli, A, Michelotti, A, Fratini, B, Saltarelli, R, Paris, I, Muratore, M, Cassano, A, Gianni, L, Gaspari, V, Veltri, E, Zoratto, F, Fiorio, E, Fabbri, M, Mazzotta, M, Ruggeri, E, Pedersini, R, Valerio, M, Filomeno, L, Minelli, M, Scavina, P, Raffaele, M, Astone, A, De Vita, R, Pozzi, M, Riccardi, F, Greco, F, Moscetti, L, Giordano, M, Maugeri-Sacca, M, Zennaro, A, Botti, C, Pelle, F, Cappelli, S, Cavicchi, F, Vizza, E, Sanguineti, G, Tomao, F, Cortesi, E, Marchetti, P, Tomao, S, Speranza, I, Sperduti, I, Ciliberto, G, Vici, P, Di Lisa F. S., Krasniqi E., Pizzuti L., Barba M., Cannita K., De Giorgi U., Borella F., Foglietta J., Cariello A., Ferro A., Picardo E., Mitidieri M., Sini V., Stani S., Tonini G., Santini D., La Verde N., Gambaro A. R., Grassadonia A., Tinari N., Garrone O., Sarobba G., Livi L., Meattini I., D'Auria G., Vergati M., Gamucci T., Pistelli M., Berardi R., Risi E., Giotta F., Lorusso V., Rinaldi L., Artale S., Cazzaniga M. E., Zustovich F., Cappuzzo F., Landi L., Torrisi R., Scagnoli S., Botticelli A., Michelotti A., Fratini B., Saltarelli R., Paris I., Muratore M., Cassano A., Gianni L., Gaspari V., Veltri E. M., Zoratto F., Fiorio E., Fabbri M. A., Mazzotta M., Ruggeri E. M., Pedersini R., Valerio M. R., Filomeno L., Minelli M., Scavina P., Raffaele M., Astone A., De Vita R., Pozzi M., Riccardi F., Greco F., Moscetti L., Giordano M., Maugeri-Sacca M., Zennaro A., Botti C., Pelle F., Cappelli S., Cavicchi F., Vizza E., Sanguineti G., Tomao F., Cortesi E., Marchetti P., Tomao S., Speranza I., Sperduti I., Ciliberto G., Vici P., Di Lisa, F, Krasniqi, E, Pizzuti, L, Barba, M, Cannita, K, De Giorgi, U, Borella, F, Foglietta, J, Cariello, A, Ferro, A, Picardo, E, Mitidieri, M, Sini, V, Stani, S, Tonini, G, Santini, D, La Verde, N, Gambaro, A, Grassadonia, A, Tinari, N, Garrone, O, Sarobba, G, Livi, L, Meattini, I, D'Auria, G, Vergati, M, Gamucci, T, Pistelli, M, Berardi, R, Risi, E, Giotta, F, Lorusso, V, Rinaldi, L, Artale, S, Cazzaniga, M, Zustovich, F, Cappuzzo, F, Landi, L, Torrisi, R, Scagnoli, S, Botticelli, A, Michelotti, A, Fratini, B, Saltarelli, R, Paris, I, Muratore, M, Cassano, A, Gianni, L, Gaspari, V, Veltri, E, Zoratto, F, Fiorio, E, Fabbri, M, Mazzotta, M, Ruggeri, E, Pedersini, R, Valerio, M, Filomeno, L, Minelli, M, Scavina, P, Raffaele, M, Astone, A, De Vita, R, Pozzi, M, Riccardi, F, Greco, F, Moscetti, L, Giordano, M, Maugeri-Sacca, M, Zennaro, A, Botti, C, Pelle, F, Cappelli, S, Cavicchi, F, Vizza, E, Sanguineti, G, Tomao, F, Cortesi, E, Marchetti, P, Tomao, S, Speranza, I, Sperduti, I, Ciliberto, G, Vici, P, Di Lisa F. S., Krasniqi E., Pizzuti L., Barba M., Cannita K., De Giorgi U., Borella F., Foglietta J., Cariello A., Ferro A., Picardo E., Mitidieri M., Sini V., Stani S., Tonini G., Santini D., La Verde N., Gambaro A. R., Grassadonia A., Tinari N., Garrone O., Sarobba G., Livi L., Meattini I., D'Auria G., Vergati M., Gamucci T., Pistelli M., Berardi R., Risi E., Giotta F., Lorusso V., Rinaldi L., Artale S., Cazzaniga M. E., Zustovich F., Cappuzzo F., Landi L., Torrisi R., Scagnoli S., Botticelli A., Michelotti A., Fratini B., Saltarelli R., Paris I., Muratore M., Cassano A., Gianni L., Gaspari V., Veltri E. M., Zoratto F., Fiorio E., Fabbri M. A., Mazzotta M., Ruggeri E. M., Pedersini R., Valerio M. R., Filomeno L., Minelli M., Scavina P., Raffaele M., Astone A., De Vita R., Pozzi M., Riccardi F., Greco F., Moscetti L., Giordano M., Maugeri-Sacca M., Zennaro A., Botti C., Pelle F., Cappelli S., Cavicchi F., Vizza E., Sanguineti G., Tomao F., Cortesi E., Marchetti P., Tomao S., Speranza I., Sperduti I., Ciliberto G., and Vici P.

Abstract

Background: In triple negative breast cancer patients treated with neoadjuvant chemotherapy, residual disease at surgery is the most relevant unfavorable prognostic factor. Current guidelines consider the use of adjuvant capecitabine, based on the results of the randomized CREATE-X study, carried out in Asian patients and including a small subset of triple negative tumors. Thus far, evidence on Caucasian patients is limited, and no real-world data are available. Methods: We carried out a multicenter, observational study, involving 44 oncologic centres. Triple negative breast cancer patients with residual disease, treated with adjuvant capecitabine from January 2017 through June 2021, were recruited. We primarily focused on treatment tolerability, with toxicity being reported as potential cause of treatment discontinuation. Secondarily, we assessed effectiveness in the overall study population and in a subset having a minimum follow-up of 2 years. Results: Overall, 270 patients were retrospectively identified. The 50.4% of the patients had residual node positive disease, 7.8% and 81.9% had large or G3 residual tumor, respectively, and 80.4% a Ki-67 >20%. Toxicity-related treatment discontinuation was observed only in 10.4% of the patients. In the whole population, at a median follow-up of 15 months, 2-year disease-free survival was 62%, 2 and 3-year overall survival 84.0% and 76.2%, respectively. In 129 patients with a median follow-up of 25 months, 2-year disease-free survival was 43.4%, 2 and 3-year overall survival 78.0% and 70.8%, respectively. Six or more cycles of capecitabine were associated with more favourable outcomes compared with less than six cycles. Conclusion: The CaRe study shows an unexpectedly good tolerance of adjuvant capecitabine in a real-world setting, although effectiveness appears to be lower than that observed in the CREATE-X study. Methodological differences between the two studies impose significant limits to comparability concerning ef

Published
2023

6. EP17.06-01 COVID-19 Long-Lasting Effect on Lung Cancer Diagnoses in Italy: Update of the Real-World Multicenter COVID-DELAY Study

Author

Mentrasti, G., primary, Cognigni, V., additional, Galassi, T., additional, Signorelli, D., additional, Pizzutilo, E.G., additional, Martinelli, F., additional, Lo Russo, G., additional, Leporati, R., additional, Ambrosini, P., additional, Giusti, R., additional, D'Amuri, S., additional, Rocco, D., additional, Della Gravara, L., additional, Antonuzzo, L., additional, Fancelli, S., additional, Gori, S., additional, Sernia, S., additional, Ferrari, M., additional, De Tursi, M., additional, Di Marino, P., additional, Di Maio, M., additional, Salerno, F., additional, Zumstein, L., additional, Russano, M., additional, Citarella, F., additional, Adamo, V., additional, Russo, A., additional, Scimone, C., additional, Sforza, V., additional, Morabito, A., additional, La Verde, N., additional, Cona, M.S., additional, Catalano, V., additional, Emili, R., additional, Sarti, D., additional, Morgillo, F., additional, Di Guida, G., additional, Rocchi, M.B.L., additional, Parisi, A., additional, and Berardi, R., additional

Published
2023
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7. Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2−) advanced breast cancer patients: New insights beyond clinical trials. The EVA study

Author

Alù, M., Ancona, C., Andreis, D., Bajardi, E., Benedetto, C., Berardi, R., Bordin, E., Butti, C., Capri, G., Cicchiello, F., Cocciolone, V., Dester, M., D'Onofrio, L., Febbraro, A., Ferrarini, I., Fotia, V., Gervasi, E., Guaitoli, G., Licata, L., Liscia, N., Mentuccia, L., Miraglio, E., Nicolini, M., Paternò, E., Pedani, F., Pellegrini, D., Petrucelli, L., De Laurentiis, M., Pizzuti, L., Pogliani, C., Riva, F., Cazzaniga, M.E., Airoldi, M., Arcangeli, V., Artale, S., Atzori, F., Ballerio, A., Bianchi, G.V., Blasi, L., Campidoglio, S., Ciccarese, M., Cursano, M.C., Piezzo, M., Fabi, A., Ferrari, L., Ferzi, A., Ficorella, C., Frassoldati, A., Fumagalli, A., Garrone, O., Gebbia, V., Generali, D., La Verde, N., Maur, M., Michelotti, A., Moretti, G., Musolino, A., Palumbo, R., Pistelli, M., Porpiglia, M., Sartori, D., Scavelli, C., Schirone, A., Turletti, A., Valerio, M.R., Vici, P., Zambelli, A., Clivio, L., and Torri, V.

Published
2017
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8. Implementation of preventive and predictive BRCA testing in patients with breast, ovarian, pancreatic, and prostate cancer: a position paper of Italian Scientific Societies

Author

Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., Tagliafico E., Russo, A, Incorvaia, L, Capoluongo, E, Tagliaferri, P, Gori, S, Cortesi, L, Genuardi, M, Turchetti, D, De Giorgi, U, Di Maio, M, Barberis, M, Dessena, M, Del Re, M, Lapini, A, Luchini, C, Jereczek-Fossa, B, Sapino, A, Cinieri, S, Beretta, G, Bella, M, Bracarda, S, Colombo, N, Conteduca, V, Del Mastro, L, Galvano, A, Gristina, V, Guarneri, V, La Verde, N, Lorusso, D, Marchetti, P, Normanno, N, Ottini, L, Pensabene, M, Pignata, S, Procopio, G, Ricevuto, E, Silvestris, N, Tassone, P, Tucci, M, Donato, V, Carrara, S, Paiella, S, Gentilini, O, Gunelli, R, Nicolis, F, Buttitta, F, Colecchia, M, Fassan, M, Malapelle, U, Marchetti, A, Marchio, C, Scarpa, A, Truini, M, Zamboni, G, Gion, M, Trevisiol, C, Gronchi, A, Danesi, R, Di Marco, V, Carrera, P, Ghiorzo, P, Pasini, B, Varesco, L, Artibani, W, Ludovico, G, Campanella, O, Vatrano, S, Tagliafico, E, Russo A., Incorvaia L., Capoluongo E., Tagliaferri P., Gori S., Cortesi L., Genuardi M., Turchetti D., De Giorgi U., Di Maio M., Barberis M., Dessena M., Del Re M., Lapini A., Luchini C., Jereczek-Fossa B. A., Sapino A., Cinieri S., Beretta G., Bella M. A., Bracarda S., Colombo N., Conteduca V., Del Mastro L., Galvano A., Gristina V., Guarneri V., La Verde N., Lorusso D., Marchetti P., Normanno N., Ottini L., Pensabene M., Pignata S., Procopio G., Ricevuto E., Silvestris N., Tassone P., Tucci M., Donato V., Carrara S., Paiella S., Gentilini O., Gunelli R., Nicolis F., Buttitta F., Colecchia M., Fassan M., Malapelle U., Marchetti A., Marchio C., Scarpa A., Truini M., Zamboni G., Gion M., Trevisiol C., Gronchi A., Danesi R., Di Marco V., Carrera P., Ghiorzo P., Pasini B., Varesco L., Artibani W., Ludovico G., Campanella O., Vatrano S., and Tagliafico E.

Abstract

Constitutional BRCA1/BRCA2 pathogenic or likely pathogenic variants (PVs) are associated with an increased risk for developing breast and ovarian cancers. Current evidence indicates that BRCA1/2 PVs are also associated with pancreatic cancer, and that BRCA2 PVs are associated with prostate cancer risk. The identification of carriers of constitutional PVs in the BRCA1/2 genes allows the implementation of individual and family prevention pathways, through validated screening programs and risk-reducing strategies. According to the relevant and increasing therapeutic predictive implications, the inclusion of BRCA testing in the routine management of patients with breast, ovarian, pancreatic and prostate cancers represent a key requirement to optimize medical or surgical therapeutic and prevention decision-making, and access to specific anticancer therapies. Therefore, accurate patient selection, the use of standardized and harmonized procedures, and adherence to homogeneous testing criteria, are essential elements to implement BRCA testing in clinical practice. This consensus position paper has been developed and approved by a multidisciplinary Expert Panel of 64 professionals on behalf of the AIOM–AIRO–AISP–ANISC–AURO–Fondazione AIOM–SIAPEC/IAP–SIBioC–SICO–SIF–SIGE–SIGU–SIU–SIURO–UROP Italian Scientific Societies, and a patient association (aBRCAdaBRA Onlus). The working group included medical, surgical and radiation oncologists, medical and molecular geneticists, clinical molecular biologists, surgical and molecular pathologists, organ specialists such as gynecologists, gastroenterologists and urologists, and pharmacologists. The manuscript is based on the expert consensus and reports the best available evidence, according to the current eligibility criteria for BRCA testing and counseling, it also harmonizes with current Italian National Guidelines and Clinical Recommendations.

Published
2022

9. Erratum to ‘Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario’: [ESMO Open Volume 7, Issue 2, April 2022, 100406](S2059702922000278)(10.1016/j.esmoop.2022.100406)

Author

Cantini L., Mentrasti G., Lo Russo G., Signorelli D., Pasello G., Rijavec E., Russano M., Antonuzzo L., Rocco D., Giusti R., Adamo V., Genova C., Tuzi A., Morabito A., Gori S., La Verde N., Chiari R., Cortellini A., Cognigni V., Pecci F., Indini A., De Toma A., Zattarin E., Oresti S., Pizzutilo E. G., Frega S., Erbetta E., Galletti A., Citarella F., Fancelli S., Caliman E., Della Gravara L., Malapelle U., Filetti M., Piras M., Toscano G., Zullo L., De Tursi M., Di Marino P., D'Emilio V., Cona M. S., Guida A., Caglio A., Salerno F., Spinelli G. P., Bennati C., Morgillo F., Russo A., Dellepiane C., Vallini I., Sforza V., Inno A., Rastelli F., Tassi V., Nicolardi L., Pensieri M. V., Emili R., Roca E., Migliore A., Galassi T., Rocchi M. B. L., Berardi R., Cantini, L., Mentrasti, G., Lo Russo, G., Signorelli, D., Pasello, G., Rijavec, E., Russano, M., Antonuzzo, L., Rocco, D., Giusti, R., Adamo, V., Genova, C., Tuzi, A., Morabito, A., Gori, S., La Verde, N., Chiari, R., Cortellini, A., Cognigni, V., Pecci, F., Indini, A., De Toma, A., Zattarin, E., Oresti, S., Pizzutilo, E. G., Frega, S., Erbetta, E., Galletti, A., Citarella, F., Fancelli, S., Caliman, E., Della Gravara, L., Malapelle, U., Filetti, M., Piras, M., Toscano, G., Zullo, L., De Tursi, M., Di Marino, P., D'Emilio, V., Cona, M. S., Guida, A., Caglio, A., Salerno, F., Spinelli, G. P., Bennati, C., Morgillo, F., Russo, A., Dellepiane, C., Vallini, I., Sforza, V., Inno, A., Rastelli, F., Tassi, V., Nicolardi, L., Pensieri, M. V., Emili, R., Roca, E., Migliore, A., Galassi, T., Rocchi, M. B. L., and Berardi, R.

Abstract

The publisher regrets that at the time the article was published the name of the author N. La Verde was mistakenly abbreviated as N.L. Verde. This has now been corrected. The publisher would like to apologise for any inconvenience caused.

Published
2022

10. The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial

Author

Pizzuti, L, Barba, M, Mazzotta, M, Krasniqi, E, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Sergi, D, Marinelli, D, Paoletti, G, Tomao, S, Botticelli, A, Marchetti, P, Tinari, N, Grassadonia, A, Valerio, M, Mirabelli, R, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Meattini, I, Pistelli, M, Giotta, F, Lorusso, V, Garufi, C, Russo, A, Cazzaniga, M, Del Medico, P, Roselli, M, Vaccaro, A, Perracchio, L, di Benedetto, A, Daralioti, T, Sperduti, I, De Maria, R, Di Leo, A, Sanguineti, G, Ciliberto, G, Vici, P, Pizzuti L., Barba M., Mazzotta M., Krasniqi E., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Sergi D., Marinelli D., Paoletti G., Tomao S., Botticelli A., Marchetti P., Tinari N., Grassadonia A., Valerio M. R., Mirabelli R., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Meattini I., Pistelli M., Giotta F., Lorusso V., Garufi C., Russo A., Cazzaniga M., Del Medico P., Roselli M., Vaccaro A., Perracchio L., di Benedetto A., Daralioti T., Sperduti I., De Maria R., Di Leo A., Sanguineti G., Ciliberto G., Vici P., Pizzuti, L, Barba, M, Mazzotta, M, Krasniqi, E, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Sergi, D, Marinelli, D, Paoletti, G, Tomao, S, Botticelli, A, Marchetti, P, Tinari, N, Grassadonia, A, Valerio, M, Mirabelli, R, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Meattini, I, Pistelli, M, Giotta, F, Lorusso, V, Garufi, C, Russo, A, Cazzaniga, M, Del Medico, P, Roselli, M, Vaccaro, A, Perracchio, L, di Benedetto, A, Daralioti, T, Sperduti, I, De Maria, R, Di Leo, A, Sanguineti, G, Ciliberto, G, Vici, P, Pizzuti L., Barba M., Mazzotta M., Krasniqi E., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Sergi D., Marinelli D., Paoletti G., Tomao S., Botticelli A., Marchetti P., Tinari N., Grassadonia A., Valerio M. R., Mirabelli R., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Meattini I., Pistelli M., Giotta F., Lorusso V., Garufi C., Russo A., Cazzaniga M., Del Medico P., Roselli M., Vaccaro A., Perracchio L., di Benedetto A., Daralioti T., Sperduti I., De Maria R., Di Leo A., Sanguineti G., Ciliberto G., and Vici P.

Abstract

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2‐positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

Published
2021

11. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study

Author

Bon, G, Pizzuti, L, Laquintana, V, Loria, R, Porru, M, Marchio, C, Krasniqi, E, Barba, M, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Barchiesi, G, Mazzotta, M, Marinelli, D, Tomao, S, Marchetti, P, Valerio, M, Mirabelli, R, Russo, A, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Giotta, F, Garufi, C, Cazzaniga, M, Del Medico, P, Roselli, M, Sanguineti, G, Sperduti, I, Sapino, A, De Maria, R, Leonetti, C, Di Leo, A, Ciliberto, G, Falcioni, R, Vici, P, Bon G., Pizzuti L., Laquintana V., Loria R., Porru M., Marchio C., Krasniqi E., Barba M., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Barchiesi G., Mazzotta M., Marinelli D., Tomao S., Marchetti P., Valerio M. R., Mirabelli R., Russo A., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Giotta F., Garufi C., Cazzaniga M., Del Medico P., Roselli M., Sanguineti G., Sperduti I., Sapino A., De Maria R., Leonetti C., Di Leo A., Ciliberto G., Falcioni R., Vici P., Bon, G, Pizzuti, L, Laquintana, V, Loria, R, Porru, M, Marchio, C, Krasniqi, E, Barba, M, Maugeri-Sacca, M, Gamucci, T, Berardi, R, Livi, L, Ficorella, C, Natoli, C, Cortesi, E, Generali, D, La Verde, N, Cassano, A, Bria, E, Moscetti, L, Michelotti, A, Adamo, V, Zamagni, C, Tonini, G, Barchiesi, G, Mazzotta, M, Marinelli, D, Tomao, S, Marchetti, P, Valerio, M, Mirabelli, R, Russo, A, Fabbri, M, D'Ostilio, N, Veltri, E, Corsi, D, Garrone, O, Paris, I, Sarobba, G, Giotta, F, Garufi, C, Cazzaniga, M, Del Medico, P, Roselli, M, Sanguineti, G, Sperduti, I, Sapino, A, De Maria, R, Leonetti, C, Di Leo, A, Ciliberto, G, Falcioni, R, Vici, P, Bon G., Pizzuti L., Laquintana V., Loria R., Porru M., Marchio C., Krasniqi E., Barba M., Maugeri-Sacca M., Gamucci T., Berardi R., Livi L., Ficorella C., Natoli C., Cortesi E., Generali D., La Verde N., Cassano A., Bria E., Moscetti L., Michelotti A., Adamo V., Zamagni C., Tonini G., Barchiesi G., Mazzotta M., Marinelli D., Tomao S., Marchetti P., Valerio M. R., Mirabelli R., Russo A., Fabbri M. A., D'Ostilio N., Veltri E., Corsi D., Garrone O., Paris I., Sarobba G., Giotta F., Garufi C., Cazzaniga M., Del Medico P., Roselli M., Sanguineti G., Sperduti I., Sapino A., De Maria R., Leonetti C., Di Leo A., Ciliberto G., Falcioni R., and Vici P.

Abstract

Background: HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods: The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results: We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in f

Published
2020

12. Is There Still a Role for Endocrine Therapy Alone in HR+/HER2- Advanced Breast Cancer Patients? Results from the Analysis of Two Data Sets of Patients Treated with High-Dose Fulvestrant as First-Line Therapy in the Real-World Setting: The EVA and GIM-13 AMBRA Studies

Author

Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Gianni, L, Michelotti, A, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, De Laurentiis, M, Atzori, F, Turletti, A, Porpiglia, M, Santini, D, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Giordano, M, Donadio, M, Biganzoli, L, Del Mastro, L, Bisagni, G, Livi, L, Natoli, C, Montemurro, F, Riccardi, F, Romagnoli, E, Marchetti, P, Torri, V, Pronzato, P, Mustacchi, G, Cazzaniga M. E., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M. R., Airoldi M., Moretti G., Ficorella C., Gianni L., Michelotti A., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G. V., Artale S., Blasi L., De Laurentiis M., Atzori F., Turletti A., Porpiglia M., Santini D., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Giordano M., Donadio M., Biganzoli L., Del Mastro L., Bisagni G., Livi L., Natoli C., Montemurro F., Riccardi F., Romagnoli E., Marchetti P., Torri V., Pronzato P., Mustacchi G., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Gianni, L, Michelotti, A, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, De Laurentiis, M, Atzori, F, Turletti, A, Porpiglia, M, Santini, D, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Giordano, M, Donadio, M, Biganzoli, L, Del Mastro, L, Bisagni, G, Livi, L, Natoli, C, Montemurro, F, Riccardi, F, Romagnoli, E, Marchetti, P, Torri, V, Pronzato, P, Mustacchi, G, Cazzaniga M. E., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M. R., Airoldi M., Moretti G., Ficorella C., Gianni L., Michelotti A., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G. V., Artale S., Blasi L., De Laurentiis M., Atzori F., Turletti A., Porpiglia M., Santini D., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Giordano M., Donadio M., Biganzoli L., Del Mastro L., Bisagni G., Livi L., Natoli C., Montemurro F., Riccardi F., Romagnoli E., Marchetti P., Torri V., Pronzato P., and Mustacchi G.

Abstract

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35-82) for the EVA and 57.8 years (range 35.0-82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1-48) and 12.4 months (range 2.9-70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Published
2020

13. Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

Author

Pizzuti, L, Krasniqi, E, Barchiesi, G, Della Giulia, M, Izzo, F, Sanguineti, G, Marchetti, P, Mazzotta, M, Giusti, R, Botticelli, A, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Iezzi, L, Tomao, S, Tomao, F, Tonini, G, Santini, D, Astone, A, Michelotti, A, De Angelis, C, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Rossi, E, Cazzaniga, M, Moscetti, L, Omarini, C, Piacentini, F, Fabbri, M, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Samaritani, R, Garufi, C, Barni, S, Mirabelli, R, Sarmiento, R, Veltri, E, D'Auria, G, Paris, I, Giotta, F, Lorusso, V, Cardillo, F, Landucci, E, Mauri, M, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Berardi, R, Pistelli, M, Fiorio, E, Cannita, K, Sini, V, D'Ostilio, N, Foglietta, J, Greco, F, Zamagni, C, Garrone, O, Di Cocco, B, Baldini, E, Livi, L, Desideri, I, Meattini, I, Sarobba, G, Del Medico, P, De Tursi, M, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Sperduti, I, Villa, A, Barba, M, Di Leo, A, Vici, P, Pizzuti L., Krasniqi E., Barchiesi G., Della Giulia M., Izzo F., Sanguineti G., Marchetti P., Mazzotta M., Giusti R., Botticelli A., Gamucci T., Natoli C., Grassadonia A., Tinari N., Iezzi L., Tomao S., Tomao F., Tonini G., Santini D., Astone A., Michelotti A., De Angelis C., Mentuccia L., Vaccaro A., Magnolfi E., Gelibter A., Magri V., Cortesi E., D'Onofrio L., Cassano A., Rossi E., Cazzaniga M., Moscetti L., Omarini C., Piacentini F., Fabbri M. A., Scinto A. F., Corsi D., Carbognin L., Bria E., La Verde N., Samaritani R., Garufi C., Barni S., Mirabelli R., Sarmiento R., Veltri E. M., D'Auria G., Paris I., Giotta F., Lorusso V., Cardillo F., Landucci E., Mauri M., Ficorella C., Roselli M., Adamo V., Ricciardi G. R. R., Russo A., Berardi R., Pistelli M., Fiorio E., Cannita K., Sini V., D'Ostilio N., Foglietta J., Greco F., Zamagni C., Garrone O., Di Cocco B., Baldini E., Livi L., Desideri I., Meattini I., Sarobba G., Del Medico P., De Tursi M., Generali D., De Maria R., Risi E., Ciliberto G., Sperduti I., Villa A., Barba M., Di Leo A., Vici P., Pizzuti, L, Krasniqi, E, Barchiesi, G, Della Giulia, M, Izzo, F, Sanguineti, G, Marchetti, P, Mazzotta, M, Giusti, R, Botticelli, A, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Iezzi, L, Tomao, S, Tomao, F, Tonini, G, Santini, D, Astone, A, Michelotti, A, De Angelis, C, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Rossi, E, Cazzaniga, M, Moscetti, L, Omarini, C, Piacentini, F, Fabbri, M, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Samaritani, R, Garufi, C, Barni, S, Mirabelli, R, Sarmiento, R, Veltri, E, D'Auria, G, Paris, I, Giotta, F, Lorusso, V, Cardillo, F, Landucci, E, Mauri, M, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Berardi, R, Pistelli, M, Fiorio, E, Cannita, K, Sini, V, D'Ostilio, N, Foglietta, J, Greco, F, Zamagni, C, Garrone, O, Di Cocco, B, Baldini, E, Livi, L, Desideri, I, Meattini, I, Sarobba, G, Del Medico, P, De Tursi, M, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Sperduti, I, Villa, A, Barba, M, Di Leo, A, Vici, P, Pizzuti L., Krasniqi E., Barchiesi G., Della Giulia M., Izzo F., Sanguineti G., Marchetti P., Mazzotta M., Giusti R., Botticelli A., Gamucci T., Natoli C., Grassadonia A., Tinari N., Iezzi L., Tomao S., Tomao F., Tonini G., Santini D., Astone A., Michelotti A., De Angelis C., Mentuccia L., Vaccaro A., Magnolfi E., Gelibter A., Magri V., Cortesi E., D'Onofrio L., Cassano A., Rossi E., Cazzaniga M., Moscetti L., Omarini C., Piacentini F., Fabbri M. A., Scinto A. F., Corsi D., Carbognin L., Bria E., La Verde N., Samaritani R., Garufi C., Barni S., Mirabelli R., Sarmiento R., Veltri E. M., D'Auria G., Paris I., Giotta F., Lorusso V., Cardillo F., Landucci E., Mauri M., Ficorella C., Roselli M., Adamo V., Ricciardi G. R. R., Russo A., Berardi R., Pistelli M., Fiorio E., Cannita K., Sini V., D'Ostilio N., Foglietta J., Greco F., Zamagni C., Garrone O., Di Cocco B., Baldini E., Livi L., Desideri I., Meattini I., Sarobba G., Del Medico P., De Tursi M., Generali D., De Maria R., Risi E., Ciliberto G., Sperduti I., Villa A., Barba M., Di Leo A., and Vici P.

Abstract

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients

Published
2020

14. Personalized and translational approach for malignant brain tumors in the era of precision medicine: the strategic contribution of an experienced neurosurgery laboratory in a modern neurosurgery and neuro-oncology department

Author

Campanella, R, Guarnaccia, L, Caroli, M, Zarino, B, Carrabba, G, La Verde, N, Gaudino, C, Rampini, A, Luzzi, S, Riboni, L, Locatelli, M, Navone, S, Marfia, G, Campanella R., Guarnaccia L., Caroli M., Zarino B., Carrabba G., La Verde N., Gaudino C., Rampini A., Luzzi S., Riboni L., Locatelli M., Navone S. E., Marfia G., Campanella, R, Guarnaccia, L, Caroli, M, Zarino, B, Carrabba, G, La Verde, N, Gaudino, C, Rampini, A, Luzzi, S, Riboni, L, Locatelli, M, Navone, S, Marfia, G, Campanella R., Guarnaccia L., Caroli M., Zarino B., Carrabba G., La Verde N., Gaudino C., Rampini A., Luzzi S., Riboni L., Locatelli M., Navone S. E., and Marfia G.

Abstract

Personalized medicine (PM) aims to optimize patient management, taking into account the individual traits of each patient. The main purpose of PM is to obtain the best response, improving health care and lowering costs. Extending traditional approaches, PM introduces novel patient-specific paradigms from diagnosis to treatment, with greater precision. In neuro-oncology, the concept of PM is well established. Indeed, every neurosurgical intervention for brain tumors has always been highly personalized. In recent years, PM has been introduced in neuro-oncology also to design and prescribe specific therapies for the patient and the patient's tumor. The huge advances in basic and translational research in the fields of genetics, molecular and cellular biology, transcriptomics, proteomics, and metabolomics have led to the introduction of PM into clinical practice. The identification of a patient's individual variation map may allow to design selected therapeutic protocols that ensure successful outcomes and minimize harmful side effects. Thus, clinicians can switch from the “one-size-fits-all” approach to PM, ensuring better patient care and high safety margin. Here, we review emerging trends and the current literature about the development of PM in neuro-oncology, considering the positive impact of innovative advanced researches conducted by a neurosurgical laboratory.

Published
2020

15. Erratum to ‘Evaluation of COVID-19 impact on DELAYing diagnostic-therapeutic pathways of lung cancer patients in Italy (COVID-DELAY study): fewer cases and higher stages from a real-world scenario’: [ESMO Open Volume 7, Issue 2, April 2022, 100406]

Author

Cantini, L., Mentrasti, G., Lo Russo, G., Signorelli, D., Pasello, G., Rijavec, E., Russano, M., Antonuzzo, L., Rocco, D., Giusti, R., Adamo, V., Genova, C., Tuzi, A., Morabito, A., Gori, S., La Verde, N., Chiari, R., Cortellini, A., Cognigni, V., Pecci, F., Indini, A., De Toma, A., Zattarin, E., Oresti, S., Pizzutilo, E.G., Frega, S., Erbetta, E., Galletti, A., Citarella, F., Fancelli, S., Caliman, E., Della Gravara, L., Malapelle, U., Filetti, M., Piras, M., Toscano, G., Zullo, L., De Tursi, M., Di Marino, P., D’Emilio, V., Cona, M.S., Guida, A., Caglio, A., Salerno, F., Spinelli, G.P., Bennati, C., Morgillo, F., Russo, A., Dellepiane, C., Vallini, I., Sforza, V., Inno, A., Rastelli, F., Tassi, V., Nicolardi, L., Pensieri, M.V., Emili, R., Roca, E., Migliore, A., Galassi, T., Rocchi, M.B.L., and Berardi, R.

Published
2022
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20. Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2−) advanced breast cancer patients: New insights beyond clinical trials. The EVA study

Author

Cicchiello, F., Riva, F., Cazzaniga, M. E., Pedani, F., Nicolini, Matteo, Butti, C., Liscia, N., Pogliani, C., Capri, Giorgia, Alu', Matteo, Febbraro, A., Petrucelli, L., D'Onofrio, L., De Laurentiis, M., Pellegrini, D., Mentuccia, L., Cocciolone, V., Miraglio, E., Bajardi, E., Dester, M., Paternò, Enrico, Guaitoli, G., Ferrarini, I., Gervasi, Elisea, Licata, L., Benedetto, C., Andreis, D., Bordin, E., Ancona, C., Pizzuti, L., Fotia, V., Berardi, R., Airoldi, M., Arcangeli, V., Artale, S., Atzori, F., Ballerio, A., Bianchi, G. V., Blasi, L., Campidoglio, S., Ciccarese, M., Cursano, M. C., Piezzo, M., Fabi, A., Ferrari, L., Ferzi, A., Ficorella, C., Frassoldati, A., Fumagalli, A., Garrone, O., Gebbia, V., Generali, D., La Verde, N., Maur, M., Michelotti, A., Moretti, G., Musolino, Anna, Palumbo, R., Pistelli, M., Porpiglia, M., Sartori, D., Scavelli, C., Schirone, A., Turletti, A., Valerio, M. R., Vici, P., Zambelli, Ruggero Astolfo, Clivio, L., Torri, V., Cicchiello, F, Riva, F, Cazzaniga, M, Pedani, F, Nicolini, M, Butti, C, Liscia, N, Pogliani, C, Capri, G, Alu, M, Febbraro, A, Petrucelli, L, D'Onofrio, L, De Laurentiis, M, Pellegrini, D, Mentuccia, L, Cocciolone, V, Miraglio, E, Bajardi, E, Dester, M, Paterno, E, Guaitoli, G, Ferrarini, I, Gervasi, E, Licata, L, Benedetto, C, Andreis, D, Bordin, E, Ancona, C, Pizzuti, L, Fotia, V, Berardi, R, Airoldi, M, Arcangeli, V, Artale, S, Atzori, F, Ballerio, A, Bianchi, G, Blasi, L, Campidoglio, S, Ciccarese, M, Cursano, M, Piezzo, M, Fabi, A, Ferrari, L, Ferzi, A, Ficorella, C, Frassoldati, A, Fumagalli, A, Garrone, O, Gebbia, V, Generali, D, La Verde, N, Maur, M, Michelotti, A, Moretti, G, Musolino, A, Palumbo, R, Pistelli, M, Porpiglia, M, Sartori, D, Scavelli, C, Schirone, A, Turletti, A, Valerio, M, Vici, P, Zambelli, A, Clivio, L, Torri, V, Cazzaniga, M. E, Bianchi, G. V, Cursano, M. C, Valerio, M. R, Torri, V., De Laurentiis, Michelino, Cicchiello, F., Riva, F., Cazzaniga, M. E., Pedani, F., Nicolini, M., Butti, C., Liscia, N., Pogliani, C., Capri, G., Alù, M., Febbraro, A., Petrucelli, L., D'Onofrio, L., De Laurentiis, M., Pellegrini, D., Mentuccia, L., Cocciolone, V., Miraglio, E., Bajardi, E., Dester, M., Paternò, E., Guaitoli, G., Ferrarini, I., Gervasi, E., Licata, L., Benedetto, C., Andreis, D., Bordin, E., Ancona, C., Pizzuti, L., Fotia, V., Berardi, R., Airoldi, M., Arcangeli, V., Artale, S., Atzori, F., Ballerio, A., Bianchi, G. V., Blasi, L., Campidoglio, S., Ciccarese, M., Cursano, M. C., Piezzo, M., Fabi, A., Ferrari, L., Ferzi, A., Ficorella, C., Frassoldati, A., Fumagalli, A., Garrone, O., Gebbia, V., Generali, D., La Verde, N., Maur, M., Michelotti, A., Moretti, G., Musolino, A., Palumbo, R., Pistelli, M., Porpiglia, M., Sartori, D., Scavelli, C., Schirone, A., Turletti, A., Valerio, M. R., Vici, P., Zambelli, A., Clivio, L., Cazzaniga, M., Ala, M., ARRIVAS BAJARDI, E., Paternã², E., Bianchi, G., Cursano, M., and Valerio, M.

Subjects
0301 basic medicine, Oncology, Receptor, ErbB-2, chemistry.chemical_compound, ErbB-2, 0302 clinical medicine, Dose-intensity, Exemestane, 80 and over, Neoplasm Metastasis, Fulvestrant, Aged, 80 and over, education.field_of_study, Advanced breast cancer, Dose-intensity, Everolimus, Fulvestrant, Hormone-receptor positive, Advanced breast cancer, Everolimus, Hormone-receptor positive, Adult, Aged, Androstadienes, Breast Neoplasms, Female, Follow-Up Studies, Humans, Middle Aged, Neoplasm Staging, Surgery, General Medicine, Everolimu, 030220 oncology & carcinogenesis, Receptor, medicine.drug, medicine.medical_specialty, Population, Socio-culturale, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Adverse effect, education, Gynecology, business.industry, fungi, Cancer, medicine.disease, Clinical trial, 030104 developmental biology, chemistry, business
Abstract

Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Results From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33–83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1–7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4–58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). Conclusions The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

Published
2017

21. NSABP FB-7: A phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer

Author

Jacobs, S, Robidoux, A, Abraham, J, Perez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolin, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, Pogue-Geile, K, Jacobs S. A., Robidoux A., Abraham J., Perez-Garcia J. M., La Verde N., Orcutt J. M., Cazzaniga M. E., Piette F., Antolin S., Aguirre E., Cortes J., Llombart-Cussac A., Di Cosimo S., Kim R. S., Feng H., Lipchik C., Lucas P. C., Srinivasan A., Wang Y., Song N., Gavin P. G., Balousek A. D., Paik S., Allegra C. J., Wolmark N., Pogue-Geile K. L., Jacobs, S, Robidoux, A, Abraham, J, Perez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolin, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, Pogue-Geile, K, Jacobs S. A., Robidoux A., Abraham J., Perez-Garcia J. M., La Verde N., Orcutt J. M., Cazzaniga M. E., Piette F., Antolin S., Aguirre E., Cortes J., Llombart-Cussac A., Di Cosimo S., Kim R. S., Feng H., Lipchik C., Lucas P. C., Srinivasan A., Wang Y., Song N., Gavin P. G., Balousek A. D., Paik S., Allegra C. J., Wolmark N., and Pogue-Geile K. L.

Abstract

Purpose: The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2+) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses. Experimental design: pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A). Pre-treatment biopsies and residual tumors were also compared to identify molecular changes. Results: The numerical pCR rate in the trastuzumab plus neratinib arm (50% [95%CI 34-66%]) was greater than that for single-targeted therapies with trastuzumab (38% [95%CI 24-54]) or neratinib (33% [95%CI 20-50]) in the overall cohort but was not statistically significant. Hormone receptor-negative (HR-) tumors had a higher pCR rate than HR+ tumors in all three treatment arms, with the highest pCR rate in the combination arm. Diarrhea was the most frequent adverse event and occurred in virtually all patients who received neratinib-based therapy. Grade 3 diarrhea was reported in 31% of patients; there were no grade 4 events. Our 8-gene signature, previously validated for trastuzumab benefit in two different clinical trials in the adjuvant setting, was correlated with pCR across all arms of NSABP FB-7. Specifically, patients predicted to receive no trastuzumab benefit had a significantly lower pCR rate than did patients predicted to receive the most benefit (P = 0.03). FCGR genotyping showed that patients who were homozygous for the Fc low-binding phenylalanine (F) allele for FCGR3A-158V/F were less likely to achieve pCR. Conclusions: Combining trastuzumab plus neratinib with paclitaxel increased the absolute pCR rate in the overall cohort and in HR- patients. The 8-gene signature, which is validated for predicting trastuzumab benefit in t

Published
2019

22. Palbociclib plus endocrine therapy in HER2 negative, hormonal receptor-positive, advanced breast cancer: A real-world experience

Author

Pizzuti, L, Giordano, A, Michelotti, A, Mazzotta, M, Natoli, C, Gamucci, T, De Angelis, C, Landucci, E, Diodati, L, Iezzi, L, Mentuccia, L, Fabbri, A, Barba, M, Sanguineti, G, Marchetti, P, Tomao, S, Mariani, L, Paris, I, Lorusso, V, Vallarelli, S, Cassano, A, Airoldi, F, Orlandi, A, Moscetti, L, Sergi, D, Sarobba, M, Tonini, G, Santini, D, Sini, V, Veltri, E, Vaccaro, A, Ferrari, L, De Tursi, M, Tinari, N, Grassadonia, A, Greco, F, Botticelli, A, La Verde, N, Zamagni, C, Rubino, D, Cortesi, E, Magri, V, Pomati, G, Scagnoli, S, Capomolla, E, Kayal, R, Scinto, A, Corsi, D, Cazzaniga, M, Laudadio, L, Forciniti, S, Mancini, M, Carbognin, L, Seminara, P, Barni, S, Samaritani, R, Roselli, M, Portarena, I, Russo, A, Ficorella, C, Cannita, K, Carpano, S, Pistelli, M, Berardi, R, De Maria, R, Sperduti, I, Ciliberto, G, Vici, P, Pizzuti L., Giordano A., Michelotti A., Mazzotta M., Natoli C., Gamucci T., De Angelis C., Landucci E., Diodati L., Iezzi L., Mentuccia L., Fabbri A., Barba M., Sanguineti G., Marchetti P., Tomao S., Mariani L., Paris I., Lorusso V., Vallarelli S., Cassano A., Airoldi F., Orlandi A., Moscetti L., Sergi D., Sarobba M. G., Tonini G., Santini D., Sini V., Veltri E., Vaccaro A., Ferrari L., De Tursi M., Tinari N., Grassadonia A., Greco F., Botticelli A., La Verde N., Zamagni C., Rubino D., Cortesi E., Magri V., Pomati G., Scagnoli S., Capomolla E., Kayal R., Scinto A. F., Corsi D., Cazzaniga M., Laudadio L., Forciniti S., Mancini M., Carbognin L., Seminara P., Barni S., Samaritani R., Roselli M., Portarena I., Russo A., Ficorella C., Cannita K., Carpano S., Pistelli M., Berardi R., De Maria R., Sperduti I., Ciliberto G., Vici P., Pizzuti, L, Giordano, A, Michelotti, A, Mazzotta, M, Natoli, C, Gamucci, T, De Angelis, C, Landucci, E, Diodati, L, Iezzi, L, Mentuccia, L, Fabbri, A, Barba, M, Sanguineti, G, Marchetti, P, Tomao, S, Mariani, L, Paris, I, Lorusso, V, Vallarelli, S, Cassano, A, Airoldi, F, Orlandi, A, Moscetti, L, Sergi, D, Sarobba, M, Tonini, G, Santini, D, Sini, V, Veltri, E, Vaccaro, A, Ferrari, L, De Tursi, M, Tinari, N, Grassadonia, A, Greco, F, Botticelli, A, La Verde, N, Zamagni, C, Rubino, D, Cortesi, E, Magri, V, Pomati, G, Scagnoli, S, Capomolla, E, Kayal, R, Scinto, A, Corsi, D, Cazzaniga, M, Laudadio, L, Forciniti, S, Mancini, M, Carbognin, L, Seminara, P, Barni, S, Samaritani, R, Roselli, M, Portarena, I, Russo, A, Ficorella, C, Cannita, K, Carpano, S, Pistelli, M, Berardi, R, De Maria, R, Sperduti, I, Ciliberto, G, Vici, P, Pizzuti L., Giordano A., Michelotti A., Mazzotta M., Natoli C., Gamucci T., De Angelis C., Landucci E., Diodati L., Iezzi L., Mentuccia L., Fabbri A., Barba M., Sanguineti G., Marchetti P., Tomao S., Mariani L., Paris I., Lorusso V., Vallarelli S., Cassano A., Airoldi F., Orlandi A., Moscetti L., Sergi D., Sarobba M. G., Tonini G., Santini D., Sini V., Veltri E., Vaccaro A., Ferrari L., De Tursi M., Tinari N., Grassadonia A., Greco F., Botticelli A., La Verde N., Zamagni C., Rubino D., Cortesi E., Magri V., Pomati G., Scagnoli S., Capomolla E., Kayal R., Scinto A. F., Corsi D., Cazzaniga M., Laudadio L., Forciniti S., Mancini M., Carbognin L., Seminara P., Barni S., Samaritani R., Roselli M., Portarena I., Russo A., Ficorella C., Cannita K., Carpano S., Pistelli M., Berardi R., De Maria R., Sperduti I., Ciliberto G., and Vici P.

Abstract

Data from 423 human epidermal growth factor receptor 2-negative (HER2−), hormone receptor-positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (p = 0.002) and favorably influenced by early line-treatment (p < 0.0001). At 6 months, median progression-free survival was 12 months (95% CI, 8–16) and median overall survival was 24 months (95% CI, 17–30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2−, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.

Published
2019

23. Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

Author

Cazzaniga, M, Danesi, R, Girmenia, C, Invernizzi, P, Elvevi, A, Uguccioni, M, Amaducci, L, Atzori, F, Blasi, L, Butti, C, Collova, E, De Conciliis, E, Fabi, A, Febbraro, A, Garrone, O, Gianni, L, Giotta, F, La Verde, N, Michelotti, A, Palumbo, R, Paris, I, Pistelli, M, Pizzuti, L, Rubino, D, Valerio, M, Zustovich, F, Cazzaniga M. E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M. R., Zustovich F., Cazzaniga, M, Danesi, R, Girmenia, C, Invernizzi, P, Elvevi, A, Uguccioni, M, Amaducci, L, Atzori, F, Blasi, L, Butti, C, Collova, E, De Conciliis, E, Fabi, A, Febbraro, A, Garrone, O, Gianni, L, Giotta, F, La Verde, N, Michelotti, A, Palumbo, R, Paris, I, Pistelli, M, Pizzuti, L, Rubino, D, Valerio, M, Zustovich, F, Cazzaniga M. E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M. R., and Zustovich F.

Abstract

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. Results: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. Conclusions: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.

Published
2019

24. Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success

Author

Cazzaniga M. E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M. R., Zustovich F., Cazzaniga M.E., Danesi R., Girmenia C., Invernizzi P., Elvevi A., Uguccioni M., Amaducci L., Atzori F., Blasi L., Butti C., Collova E., De Conciliis E., Fabi A., Febbraro A., Garrone O., Gianni L., Giotta F., La Verde N., Michelotti A., Palumbo R., Paris I., Pistelli M., Pizzuti L., Rubino D., Valerio M.R., Zustovich F., Cazzaniga, M, Danesi, R, Girmenia, C, Invernizzi, P, Elvevi, A, Uguccioni, M, Amaducci, L, Atzori, F, Blasi, L, Butti, C, Collova, E, De Conciliis, E, Fabi, A, Febbraro, A, Garrone, O, Gianni, L, Giotta, F, La Verde, N, Michelotti, A, Palumbo, R, Paris, I, Pistelli, M, Pizzuti, L, Rubino, D, Valerio, M, and Zustovich, F

Subjects
0301 basic medicine, Cancer Research, Review, Disease, chemistry.chemical_compound, 0302 clinical medicine, Ribociclib, Molecular Targeted Therapy, Abemaciclib, Clinical Trials as Topic, Disease Management, Metastatic breast cancer, Everolimu, Oncology, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, Advanced breast cancer, Receptors, Progesterone, Breast Neoplasm, medicine.drug, Human, medicine.medical_specialty, Neutropenia, Drug-Related Side Effects and Adverse Reactions, Antineoplastic Agents, Hormonal, Protein Kinase Inhibitor, Breast Neoplasms, Palbociclib, 03 medical and health sciences, Breast cancer, medicine, Biomarkers, Tumor, Humans, Everolimus, Intensive care medicine, Adverse effect, Protein Kinase Inhibitors, business.industry, medicine.disease, Clinical trial, 030104 developmental biology, chemistry, MED/06 - ONCOLOGIA MEDICA, business, Drug-Related Side Effects and Adverse Reaction
Abstract

Purpose: Agents targeting HR-positive, HER2-negative locally advanced or metastatic breast cancer have improved patient outcomes compared with conventional single-agent endocrine therapy. Currently, approved targeted agents include everolimus and three CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib. Unlike the well-characterized and easily manageable safety profile of endocrine therapies, adverse events associated with targeted therapies are complex and potentially severe. Their prompt recognition and treatment, crucial for prolonged endocrine sensitivity and survival, may be challenging and requires a multidisciplinary effort and a good knowledge of drug interactions. Methods: We reviewed the current evidence on the drug safety of targeted agents for metastatic breast cancer currently used in clinical practice in Italy, supported by the clinical experience of Italian oncologists with expertise in the field. Results: All oncologists had used CDK4/6 inhibitors in clinical practice and/or within a clinical trial. The clinical management of toxicities, including dose adjustments, treatment interruptions, and concerns regarding special populations is discussed, and the management of relevant adverse events, related to individual agents and class-specific, toxicities is reviewed. Hematologic toxicities have the greatest impact on clinical management of the disease and on patients. Although toxicities associated with the new treatments result in more visits to the physician and more time and attention with patients, they are manageable, with no need for the oncologist to consult with specialist physicians. Conclusions: Based on the available evidence and current guidelines, we propose a series of practical recommendations for multidisciplinary clinical management of the various toxicities associated with the addition of targeted agents to endocrine therapy.

Published
2019

26. 1616P Drop in early-stage colorectal cancer diagnoses after COVID-19: Preliminary report from the COVID-DELAY study

Author

Mentrasti, G., primary, Cognigni, V., additional, Di Maio, M., additional, Chiari, R., additional, La Verde, N., additional, Zichi, C., additional, Aimar, G., additional, De Vita, F., additional, Marini, S., additional, Cona, M.S., additional, Pinterpe, G., additional, Pecci, F., additional, Migliore, A., additional, Caravita, E., additional, Rocchi, M.B.L., additional, Bittoni, A., additional, Giampieri, R., additional, Cantini, L., additional, and Berardi, R., additional

Published
2021
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27. 1609P COVID-19 outbreak repercussions on breast cancer diagnoses and access to treatment: Preliminary data from the COVID-DELAY study

Author

Berardi, R., primary, Mentrasti, G., additional, Crocetti, S., additional, La Verde, N., additional, Chiari, R., additional, Cona, M.S., additional, Nicolardi, L., additional, De Filippis, C., additional, Oldani, S., additional, Pecci, F., additional, Venanzi, F., additional, Rocchi, M.B.L., additional, Savini, A., additional, Cantini, L., additional, and Pistelli, M., additional

Published
2021
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28. The prognostic relevance of HER2-positivity gain in metastatic breast cancer in the ChangeHER trial

Author

Pizzuti, L., Barba, M., Mazzotta, M., Krasniqi, E., Maugeri-Sacca, M., Gamucci, T., Berardi, R., Livi, L., Ficorella, C., Natoli, C., Cortesi, E., Generali, D., La Verde, N., Cassano, A., Bria, Emilio, Moscetti, L., Michelotti, A., Adamo, V., Zamagni, C., Tonini, G., Sergi, D., Marinelli, D., Paoletti, G., Tomao, S., Botticelli, A., Marchetti, P., Tinari, N., Grassadonia, A., Valerio, M. R., Mirabelli, R., Fabbri, M. A., D'Ostilio, N., Veltri, E., Corsi, Domenico Cristiano, Garrone, O., Paris, Ida, Sarobba, G., Meattini, I., Pistelli, M., Giotta, F., Lorusso, V., Garufi, C., Russo, A., Cazzaniga, M., Del Medico, P., Roselli, M., Vaccaro, A., Perracchio, L., di Benedetto, A., Daralioti, T., Sperduti, I., De Maria Marchiano, Ruggero, Di Leo, A., Sanguineti, G., Ciliberto, G., Vici, P., Bria E. (ORCID:0000-0002-2333-704X), Corsi D., Paris I., De Maria R. (ORCID:0000-0003-2255-0583), Pizzuti, L., Barba, M., Mazzotta, M., Krasniqi, E., Maugeri-Sacca, M., Gamucci, T., Berardi, R., Livi, L., Ficorella, C., Natoli, C., Cortesi, E., Generali, D., La Verde, N., Cassano, A., Bria, Emilio, Moscetti, L., Michelotti, A., Adamo, V., Zamagni, C., Tonini, G., Sergi, D., Marinelli, D., Paoletti, G., Tomao, S., Botticelli, A., Marchetti, P., Tinari, N., Grassadonia, A., Valerio, M. R., Mirabelli, R., Fabbri, M. A., D'Ostilio, N., Veltri, E., Corsi, Domenico Cristiano, Garrone, O., Paris, Ida, Sarobba, G., Meattini, I., Pistelli, M., Giotta, F., Lorusso, V., Garufi, C., Russo, A., Cazzaniga, M., Del Medico, P., Roselli, M., Vaccaro, A., Perracchio, L., di Benedetto, A., Daralioti, T., Sperduti, I., De Maria Marchiano, Ruggero, Di Leo, A., Sanguineti, G., Ciliberto, G., Vici, P., Bria E. (ORCID:0000-0002-2333-704X), Corsi D., Paris I., and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

In metastatic breast cancer (mBC), the change of human epidermal growth factor receptor 2 (HER2) status between primary and metastatic lesions is widely recognized, however clinical implications are unknown. Our study address the question if relevant differences exist between subjects who preserve the HER2 status and those who gain the HER2 positivity when relapsed. Data of patients affected by HER2-positive mBC, treated with pertuzumab and/or trastuzumab-emtansine (T-DM1) in a real-world setting at 45 Italian cancer centers were retrospectively collected and analyzed. From 2003 to 2017, 491 HER2‐positive mBC patients were included. Of these, 102 (20.7%) had been initially diagnosed as HER2-negative early BC. Estrogen and/or progesterone receptor were more expressed in patients with HER2-discordance compared to patients with HER2-concordant status (p < 0.0001 and p = 0.006, respectively). HER2-discordant tumors were characterized also by a lower rate of brain metastases (p = 0.01) and a longer disease free interval (p < 0.0001). Median overall survival was longer, although not statistically significant, in the subgroup of patients with HER2-discordant cancer with respect to patients with HER2-concordant status (140 vs 78 months, p = 0.07). Our findings suggest that patients with HER2-positive mBC with discordant HER2 status in early BC may have different clinical, biological and prognostic behavior compared to HER2-concordant patients.

Published
2021

30. Everolimus (EVE) and exemestane (EXE) in patients with advanced breast cancer aged ≥ 65 years: New lessons for clinical practice from the EVA study

Author

Cazzaniga, M., Verusio, C., Ciccarese, M., Fumagalli, A., Sartori, D., Ancona, C., Airoldi, M., Moretti, G., Ficorella, C., Arcangeli, V., Diodati, L., Zambelli, A., Febbraro, A., Generali, D., Pistelli, M., Garrone, O., Musolino, A., Vici, P., Maur, M., Mentuccia, L., La Verde, N., Bianchi, G., Artale, S., Blasi, L., Piezzo, M., Atzori, F., Turletti, A., Benedetto, C., Cursano, M. C., Fabi, A., Gebbia, V., Schirone, A., Palumbo, R., Ferzi, A., Frassoldati, A., Scavelli, C., Clivio, L., Torri, V., On behalf of The EVA Study Group, Cazzaniga, Marina, Verusio, Claudio, Ciccarese, Mariangela, Fumagalli, Alberto, Sartori, Donata, D'Ancona, Cristina, Airoldi, Mario, Moretti, Gabriella, Ficorella, Corrado, Arcangeli, Valentina, Diodati, Lucrezia, Zambelli, Alberto, Febbraro, Antonio, Generali, Daniele, Pistelli, Mirco, Garrone, Ornella, Musolino, Antonino, Vici, Patrizia, Maur, Michela, Mentuccia, Lucia, La Verde, Nicla, Bianchi, Giulia, Artale, Salvatore, Blasi, Livio, Piezzo, Matilde, Atzori, Francesco, Turletti, Anna, Benedetto, Chiara, Cursano, Maria Concetta, Fabi, Alessandra, Gebbia, Vittorio, Schirone, Antonio, Palumbo, Raffaella, Ferzi, Antonella, Frassoldati, Antonio, Scavelli, Claudio, Clivio, Luca, Torri, Valter, Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Ancona, C, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, On behalf of The EVA Study, G, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio MR., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M.C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Torri V., and On behalf of The EVA Study Group

Subjects
medicine.medical_specialty, Socio-culturale, Hormone-receptor positive, Exemestane, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Breast cancer, Elderly, Weight loss, Internal medicine, Advanced breast cancer, Everolimus, Oncology, medicine, 030212 general & internal medicine, Stomatitis, Pneumonitis, business.industry, Cancer, medicine.disease, Rash, Everolimu, chemistry, 030220 oncology & carcinogenesis, MED/06 - ONCOLOGIA MEDICA, medicine.symptom, business, Research Paper, medicine.drug
Abstract

BACKGROUND: The present analysis focuses on real-world data of Everolimus- Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years. METHODS: Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and [greater than or equal to] 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel- Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model. RESULTS: From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged [greater than or equal to] 65 years, of whom 87 were [greater than or equal to] 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged [greater than or equal to] 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (> 7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3-4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged [greater than or equal to] 70 years. Five treatment-related deaths were collected (3,2%). CONCLUSIONS: EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones.

Published
2018

31. 35P Lung cancer diagnosis and continuum of care: How did the COVID-19 outbreak impact? Data from an Italian multicenter study

Author

Cantini, L., primary, Mentrasti, G., additional, La Verde, N., additional, Cona, M.S., additional, Chiari, R., additional, Martinelli, E., additional, Morgillo, F., additional, Nicolardi, L., additional, Cortellini, A., additional, Pensieri, V., additional, Cognigni, V., additional, Pinterpe, G., additional, Galassi, T., additional, Pecci, F., additional, Mazzanti, P., additional, Di Pietro Paolo, M., additional, Giampieri, R., additional, and Berardi, R., additional

Published
2021
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32. Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Author

De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., Zoboli A., De Placido, S, Gallo, C, De Laurentiis, M, Bisagni, G, Arpino, G, Sarobba, M, Riccardi, F, Russo, A, Del Mastro, L, Cogoni, A, Cognetti, F, Gori, S, Foglietta, J, Frassoldati, A, Amoroso, D, Laudadio, L, Moscetti, L, Montemurro, F, Verusio, C, Bernardo, A, Lorusso, V, Gravina, A, Moretti, G, Lauria, R, Lai, A, Mocerino, C, Rizzo, S, Nuzzo, F, Carlini, P, Perrone, F, Accurso, A, Agostara, B, Aieta, M, Alabiso, O, Alicicco, M, Amadori, D, Amaducci, L, Amiconi, G, Antuzzi, G, Ardine, M, Ardizzoia, A, Aversa, C, Badalamenti, G, Barni, S, Basurto, C, Berardi, R, Bergamasco, C, Bidoli, P, Bighin, C, Biondi, E, Boni, C, Borgonovo, K, Botta, M, Bravi, S, Bruzzi, P, Buono, G, Butera, A, Caldara, A, Candeloro, G, Cappelletti, C, Cardalesi, C, Carfora, E, Cariello, A, Carrozza, F, Carteni, G, Caruso, M, Casadei, V, Casanova, C, Castori, L, Cavanna, L, Cavazzini, G, Cazzaniga, M, Chilelli, M, Chiodini, P, Chiorrini, S, Ciardiello, F, Ciccarese, M, Cinieri, S, Clerico, M, Coccaro, M, Comande, M, Corbo, C, Cortino, G, Cusenza, S, Daniele, G, D'Arco, A, D'Auria, G, Dazzi, C, De Angelis, C, de Braud, F, De Feo, G, De Matteis, A, De Tursi, M, Di Blasio, A, di Lucca, G, Di Lullo, L, Di Rella, F, Di Renzo, G, Di Stefano, P, Di Stefano, A, Diana, A, Donati, S, Fabbri, A, Fabi, A, Faedi, M, Farina, G, Farris, A, Febbraro, A, Fedele, P, Federico, P, Ferrau, F, Ferretti, G, Ferro, A, Floriani, I, Forcignano, R, Forciniti, S, Forestieri, V, Fornari, G, Frisinghelli, M, Fusco, V, Gallizzi, G, Galvano, A, Gambardella, A, Gambi, A, Gebbia, V, Gervasi, E, Ghilardi, M, Giacobino, A, Giardina, G, Giotta, F, Giraudi, S, Giuliano, M, Grassadonia, A, Grasso, D, Grosso, F, Guizzaro, L, Incoronato, P, Incorvaia, L, Iodice, G, La Verde, N, Labonia, V, Landi, G, Latorre, A, Leonardi, V, Levaggi, A, Limite, G, Lina Bascialla, L, Livi, L, Maiello, E, Mandelli, D, Marcon, I, Menon, D, Montedoro, M, Moraca, L, Moretti, A, Morritti, M, Morselli, P, Mura, A, Mura, S, Musacchio, M, Muzio, A, Natale, D, Natoli, C, Nigro, C, Nistico, C, Nuzzo, A, Orditura, M, Orlando, L, Pacilio, C, Palumbo, G, Palumbo, R, Pasini, F, Paterno, E, Pazzola, A, Pelliccioni, S, Pensabene, M, Perroni, D, Pesenti Gritti, A, Petrelli, F, Piccirillo, M, Pinotti, G, Pogliani, C, Poli, D, Prader, S, Recchia, F, Rizzi, D, Romano, C, Rossello, R, Rossini, C, Salvucci, G, Sanna, V, Santini, A, Saracchini, S, Savastano, C, Scambia, G, Schettini, F, Schiavone, P, Schirone, A, Seles, E, Signoriello, S, Signoriello, G, Silva, R, Silvestri, A, Simeon, V, Spagnoletti, I, Tamberi, S, Teragni, C, Thalmann, V, Thomas, R, Thomas, G, Tienghi, A, Tinari, N, Tinessa, V, Tomei, F, Tonini, G, Torri, V, Traficante, D, Tudini, M, Turazza, M, Vignoli, R, Vitale, M, Zacchia, A, Zagarese, P, Zanni, A, Zavallone, L, Zavettieri, M, Zoboli, A, De Placido S., Gallo C., De Laurentiis M., Bisagni G., Arpino G., Sarobba M. G., Riccardi F., Russo A., Del Mastro L., Cogoni A. A., Cognetti F., Gori S., Foglietta J., Frassoldati A., Amoroso D., Laudadio L., Moscetti L., Montemurro F., Verusio C., Bernardo A., Lorusso V., Gravina A., Moretti G., Lauria R., Lai A., Mocerino C., Rizzo S., Nuzzo F., Carlini P., Perrone F., Accurso A., Agostara B., Aieta M., Alabiso O., Alicicco M. G., Amadori D., Amaducci L., Amiconi G., Antuzzi G., Ardine M., Ardizzoia A., Aversa C., Badalamenti G., Barni S., Basurto C., Berardi R., Bergamasco C., Bidoli P., Bighin C., Biondi E., Boni C., Borgonovo K., Botta M., Bravi S., Bruzzi P., Buono G., Butera A., Caldara A., Candeloro G., Cappelletti C., Cardalesi C., Carfora E., Cariello A., Carrozza F., Carteni G., Caruso M., Casadei V., Casanova C., Castori L., Cavanna L., Cavazzini G., Cazzaniga M., Chilelli M., Chiodini P., Chiorrini S., Ciardiello F., Ciccarese M., Cinieri S., Clerico M., Coccaro M., Comande M., Corbo C., Cortino G., Cusenza S., Daniele G., D'arco A. M., D'auria G., Dazzi C., De Angelis C., de Braud F., De Feo G., De Matteis A., De Tursi M., Di Blasio A., di Lucca G., Di Lullo L., Di Rella F., Di Renzo G., Di Stefano P., Di Stefano A., Diana A., Donati S., Fabbri A., Fabi A., Faedi M., Farina G., Farris A., Febbraro A., Fedele P., Federico P., Ferrau F., Ferretti G., Ferro A., Floriani I., Forcignano R., Forciniti S., Forestieri V., Fornari G., Frisinghelli M., Fusco V., Gallizzi G., Galvano A., Gambardella A., Gambi A., Gebbia V., Gervasi E., Ghilardi M., Giacobino A., Giardina G., Giotta F., Giraudi S., Giuliano M., Grassadonia A., Grasso D., Grosso F., Guizzaro L., Incoronato P., Incorvaia L., Iodice G., La Verde N., Labonia V., Landi G., Latorre A., Leonardi V., Levaggi A., Limite G., Lina Bascialla L., Livi L., Maiello E., Mandelli D., Marcon I., Menon D., Montedoro M., Moraca L., Moretti A., Morritti M. G., Morselli P., Mura A., Mura S., Musacchio M., Muzio A., Natale D., Natoli C., Nigro C., Nistico C., Nuzzo A., Orditura M., Orlando L., Pacilio C., Palumbo G., Palumbo R., Pasini F., Paterno E., Pazzola A., Pelliccioni S., Pensabene M., Perroni D., Pesenti Gritti A., Petrelli F., Piccirillo M. C., Pinotti G., Pogliani C., Poli D., Prader S., Recchia F., Rizzi D., Romano C., Rossello R., Rossini C., Salvucci G., Sanna V., Santini A., Saracchini S., Savastano C., Scambia G., Schettini F., Schiavone P., Schirone A., Seles E., Signoriello S., Signoriello G., Silva R. R., Silvestri A., Simeon V., Spagnoletti I., Tamberi S., Teragni C., Thalmann V., Thomas R., Thomas G., Tienghi A., Tinari N., Tinessa V., Tomei F., Tonini G., Torri V., Traficante D., Tudini M., Turazza M., Vignoli R., Vitale M. G., Zacchia A., Zagarese P., Zanni A., Zavallone L., Zavettieri M., and Zoboli A.

Abstract

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is regist

Published
2018

33. Everolimus (EVE) and exemestane (EXE) in patients with advanced breast cancer aged ≥ 65 years: New lessons for clinical practice from the EVA study

Author

Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Ancona, C, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, On behalf of The EVA Study, G, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Ancona C., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M. C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Torri V., On behalf of The EVA Study Group, Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Ancona, C, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, On behalf of The EVA Study, G, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Ancona C., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M. C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Torri V., and On behalf of The EVA Study Group

Abstract

BACKGROUND: The present analysis focuses on real-world data of Everolimus- Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years. METHODS: Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and [greater than or equal to] 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel- Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model. RESULTS: From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged [greater than or equal to] 65 years, of whom 87 were [greater than or equal to] 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged [greater than or equal to] 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (> 7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3-4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged [greater than or equal to] 70 years. Five treatment-related deaths were collected (3,2%). CONCLUSIONS: EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones.

Published
2018

34. Correction: Everolimus (Eve) and exemestane (EXE) in patients with advanced breast cancer aged ≥ 65 years: New lessons for clinical practice from the EVA study (Oncotarget (2018) 9:77 (34639-34640) DOI: 10.18632/oncotarget.25874)

Author

Cazzaniga M., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M. R., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M. C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Torri V., Cazzaniga M., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M. R., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M. C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., and Torri V.

Abstract

This article has been corrected: The correct author names are given below: Chiara Ancona and Michela Piezzo.

Published
2018

35. Erratum: Everolimus (EVE) and exemestane (EXE) in patients with advanced breast cancer aged ≥ 65 years: New lessons for clinical practice from the EVA study (Oncotarget (2018) 9 (31877-31887) DOI: 10.18632/oncotarget.25874)

Author

Cazzaniga M., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M. R., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M. C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., Torri V., Cazzaniga M., Cazzaniga, M, Verusio, C, Ciccarese, M, Fumagalli, A, Sartori, D, Valerio, M, Airoldi, M, Moretti, G, Ficorella, C, Arcangeli, V, Diodati, L, Zambelli, A, Febbraro, A, Generali, D, Pistelli, M, Garrone, O, Musolino, A, Vici, P, Maur, M, Mentuccia, L, La Verde, N, Bianchi, G, Artale, S, Blasi, L, Piezzo, M, Atzori, F, Turletti, A, Benedetto, C, Cursano, M, Fabi, A, Gebbia, V, Schirone, A, Palumbo, R, Ferzi, A, Frassoldati, A, Scavelli, C, Clivio, L, Torri, V, Cazzaniga M., Verusio C., Ciccarese M., Fumagalli A., Sartori D., Valerio M. R., Airoldi M., Moretti G., Ficorella C., Arcangeli V., Diodati L., Zambelli A., Febbraro A., Generali D., Pistelli M., Garrone O., Musolino A., Vici P., Maur M., Mentuccia L., La Verde N., Bianchi G., Artale S., Blasi L., Piezzo M., Atzori F., Turletti A., Benedetto C., Cursano M. C., Fabi A., Gebbia V., Schirone A., Palumbo R., Ferzi A., Frassoldati A., Scavelli C., Clivio L., and Torri V.

Abstract

This article has been corrected: The correct author name is given below:.

Published
2018

36. NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer (vol 21, 133, 2019)

Author

Jacobs, S, Robidoux, A, Abraham, J, Perez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolin, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, and Pogue-Geile, K

Published
2020

37. Correction to: NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer

Author

Jacobs, S, Robidoux, A, Abraham, J, Pérez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolín, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, Pogue-Geile, K, Jacobs, Samuel A, Robidoux, André, Abraham, Jame, Pérez-Garcia, José Manuel, La Verde, Nicla, Orcutt, James M, Cazzaniga, Marina E, Piette, Fanny, Antolín, Silvia, Aguirre, Elena, Cortes, Javier, Llombart-Cussac, Antonio, Di Cosimo, Serena, Kim, Rim S, Feng, Huichen, Lipchik, Corey, Lucas, Peter C, Srinivasan, Ashok, Wang, Ying, Song, Nan, Gavin, Patrick G, Balousek, April D, Paik, Soonmyung, Allegra, Carmen J, Wolmark, Norman, Pogue-Geile, Katherine L, Jacobs, S, Robidoux, A, Abraham, J, Pérez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolín, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, Pogue-Geile, K, Jacobs, Samuel A, Robidoux, André, Abraham, Jame, Pérez-Garcia, José Manuel, La Verde, Nicla, Orcutt, James M, Cazzaniga, Marina E, Piette, Fanny, Antolín, Silvia, Aguirre, Elena, Cortes, Javier, Llombart-Cussac, Antonio, Di Cosimo, Serena, Kim, Rim S, Feng, Huichen, Lipchik, Corey, Lucas, Peter C, Srinivasan, Ashok, Wang, Ying, Song, Nan, Gavin, Patrick G, Balousek, April D, Paik, Soonmyung, Allegra, Carmen J, Wolmark, Norman, and Pogue-Geile, Katherine L

Abstract

After the publication [1] the authors report corrections for Table 3, for the headers of columns 5 and 7, which should read as follows: Column 5 Header: P-value for pCR, T vs Other Arms in HR+, and Column 7 Header: P-value for pCR, T vs Other Arms in HR-. The correct version of the table can be found below. (Table presented).

Published
2020

38. Correction: NSABP FB-7: A phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer (Breast Cancer Research (2019) 21 (133) DOI: 10.1186/s13058-019-1196-y)

Author

Jacobs, Samuel A, Jacobs, S, Robidoux, A, Abraham, J, Pérez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolín, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, Pogue-Geile, K, Jacobs, Samuel A, Robidoux, André, Abraham, Jame, Pérez-Garcia, José Manuel, La Verde, Nicla, Orcutt, James M, Cazzaniga, Marina E, Piette, Fanny, Antolín, Silvia, Aguirre, Elena, Cortes, Javier, Llombart-Cussac, Antonio, Di Cosimo, Serena, Kim, Rim S, Feng, Huichen, Lipchik, Corey, Lucas, Peter C, Srinivasan, Ashok, Wang, Ying, Song, Nan, Gavin, Patrick G, Balousek, April D, Paik, Soonmyung, Allegra, Carmen J, Wolmark, Norman, Pogue-Geile, Katherine L, Jacobs, Samuel A, Jacobs, S, Robidoux, A, Abraham, J, Pérez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolín, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, Pogue-Geile, K, Jacobs, Samuel A, Robidoux, André, Abraham, Jame, Pérez-Garcia, José Manuel, La Verde, Nicla, Orcutt, James M, Cazzaniga, Marina E, Piette, Fanny, Antolín, Silvia, Aguirre, Elena, Cortes, Javier, Llombart-Cussac, Antonio, Di Cosimo, Serena, Kim, Rim S, Feng, Huichen, Lipchik, Corey, Lucas, Peter C, Srinivasan, Ashok, Wang, Ying, Song, Nan, Gavin, Patrick G, Balousek, April D, Paik, Soonmyung, Allegra, Carmen J, Wolmark, Norman, and Pogue-Geile, Katherine L

Abstract

After the publication [1] the authors report corrections for Table 3, for the headers of columns 5 and 7, which should read as follows: Column 5 Header: P-value for pCR, T vs Other Arms in HR+, and Column 7 Header: P-value for pCR, T vs Other Arms in HR-. The correct version of the table can be found below. (Table presented).

Published
2020

39. Tumor-educated platelets and angiogenesis in glioblastoma : another brick in the wall for novel prognostic and targetable biomarkers, changing the vision from a localized tumor to a systemic pathology

Author

Campanella, R, Guarnaccia, L, Cordiglieri, C, Trombetta, E, Caroli, M, Carrabba, G, La Verde, N, Rampini, P, Gaudino, C, Costa, A, Luzzi, S, Mantovani, G, Locatelli, M, Riboni, L, Navone, S, Marfia, G, Campanella, Rolando, Guarnaccia, Laura, Cordiglieri, Chiara, Trombetta, Elena, Caroli, Manuela, Carrabba, Giorgio, La Verde, Nicla, Rampini, Paolo, Gaudino, Chiara, Costa, Antonella, Luzzi, Sabino, Mantovani, Giovanna, Locatelli, Marco, Riboni, Laura, Navone, Stefania Elena, Marfia, Giovanni, Campanella, R, Guarnaccia, L, Cordiglieri, C, Trombetta, E, Caroli, M, Carrabba, G, La Verde, N, Rampini, P, Gaudino, C, Costa, A, Luzzi, S, Mantovani, G, Locatelli, M, Riboni, L, Navone, S, Marfia, G, Campanella, Rolando, Guarnaccia, Laura, Cordiglieri, Chiara, Trombetta, Elena, Caroli, Manuela, Carrabba, Giorgio, La Verde, Nicla, Rampini, Paolo, Gaudino, Chiara, Costa, Antonella, Luzzi, Sabino, Mantovani, Giovanna, Locatelli, Marco, Riboni, Laura, Navone, Stefania Elena, and Marfia, Giovanni

Abstract

Circulating platelets (PLTs) are able to affect glioblastoma (GBM) microenvironment by supplying oncopromoter and pro-angiogenic factors. Among these mediators, sphingosine-1-phophate (S1P) has emerged as a potent bioactive lipid enhancing cell proliferation and survival. Here, we investigated the effect of “tumor education”, characterizing PLTs from GBM patients in terms of activation state, protein content, and pro-angiogenic potential. PLTs from healthy donors (HD-PLTs) and GBM patients (GBM-PLTs) were collected, activated, and analyzed by flow cytometry, immunofluorescence, and Western blotting. To assess the pro-angiogenic contribution of GBM-PLTs, a functional cord formation assay was performed on GBM endothelial cells (GECs) with PLT-releasate. GBM-PLTs expressed higher positivity for P-selectin compared to HD-PLTs, both in basal conditions and after stimulation with adenosine triphosphate (ADP) and thrombin receptor activating peptide (TRAP). PLTs showed higher expression of VEGFR-1, VEGFR-2, VWF, S1P, S1PR1, SphK1, and SPNS. Interestingly, increased concentrations of VEGF and its receptors VEGFR1 and VEGFR2, VWF, and S1P were found in GBM-PLT-releasate with respect to HD-PLTs. Finally, GBM-PLT-releasate showed a pro-angiogenic effect on GECs, increasing the vascular network’s complexity. Overall, our results demonstrated the contribution of PLTs to GBM angiogenesis and aggressiveness, advancing the potential of an anti-PLT therapy and the usefulness of PLT cargo as predictive and monitoring biomarkers.

Published
2020

40. Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine. Real-world evidence

Author

Krasniqi, E, Pizzuti, L, Barchiesi, G, Sergi, D, Carpano, S, Botti, C, Kayal, R, Sanguineti, G, Marchetti, P, Botticelli, A, Marinelli, D, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Tomao, S, Tonini, G, Santini, D, Michelotti, A, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Cazzaniga, M, Moscetti, L, Fabbri, A, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Garufi, C, Di Stefano, P, Mirabelli, R, Veltri, E, Paris, I, Giotta, F, Lorusso, V, Landucci, E, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Valerio, M, Berardi, R, Pistelli, M, Cannita, K, Zamagni, C, Garrone, O, Baldini, E, Livi, L, Meattini, I, Del Medico, P, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Villa, A, Sperduti, I, Mazzotta, M, Barba, M, Giordano, A, Vici, P, Krasniqi, Eriseld, Pizzuti, Laura, Barchiesi, Giacomo, Sergi, Domenico, Carpano, Silvia, Botti, Claudio, Kayal, Ramy, Sanguineti, Giuseppe, Marchetti, Paolo, Botticelli, Andrea, Marinelli, Daniele, Gamucci, Teresa, Natoli, Clara, Grassadonia, Antonino, Tinari, Nicola, Tomao, Silverio, Tonini, Giuseppe, Santini, Daniele, Michelotti, Aandrea, Mentuccia, Lucia, Vaccaro, Aangela, Magnolfi, Emanuela, Gelibter, Alain, Magri, Valentina, Cortesi, Enrico, D'Onofrio, Loretta, Cassano, Alessandra, Cazzaniga, Marina, Moscetti, Luca, Fabbri, Agnese, Scinto, Angelo Fedele, Corsi, Domenico, Carbognin, Luisa, Bria, Emilio, La Verde, Nicla, Garufi, Carlo, Di Stefano, Pia, Mirabelli, Rossana, Veltri, Enzo, Paris, Ida, Giotta, Francesco, Lorusso, Vito, Landucci, Elisa, Ficorella, Corrado, Roselli, Mario, Adamo, Vincenzo, Ricciardi, Giuseppina, Russo, Antonio, Valerio, Maria Rosaria, Berardi, Rossana, Pistelli, Mirco, Cannita, Katia, Zamagni, Claudio, Garrone, Ornella, Baldini, Editta, Livi, Lorenzo, Meattini, Icro, Del Medico, Pietro, Generali, Daniele, De Maria, Ruggero, Risi, Emanuela, Ciliberto, Gennaro, Villa, Alice, Sperduti, Isabella, Mazzotta, Marco, Barba, Maddalena, Giordano, Antonio, Vici, Patrizia, Krasniqi, E, Pizzuti, L, Barchiesi, G, Sergi, D, Carpano, S, Botti, C, Kayal, R, Sanguineti, G, Marchetti, P, Botticelli, A, Marinelli, D, Gamucci, T, Natoli, C, Grassadonia, A, Tinari, N, Tomao, S, Tonini, G, Santini, D, Michelotti, A, Mentuccia, L, Vaccaro, A, Magnolfi, E, Gelibter, A, Magri, V, Cortesi, E, D'Onofrio, L, Cassano, A, Cazzaniga, M, Moscetti, L, Fabbri, A, Scinto, A, Corsi, D, Carbognin, L, Bria, E, La Verde, N, Garufi, C, Di Stefano, P, Mirabelli, R, Veltri, E, Paris, I, Giotta, F, Lorusso, V, Landucci, E, Ficorella, C, Roselli, M, Adamo, V, Ricciardi, G, Russo, A, Valerio, M, Berardi, R, Pistelli, M, Cannita, K, Zamagni, C, Garrone, O, Baldini, E, Livi, L, Meattini, I, Del Medico, P, Generali, D, De Maria, R, Risi, E, Ciliberto, G, Villa, A, Sperduti, I, Mazzotta, M, Barba, M, Giordano, A, Vici, P, Krasniqi, Eriseld, Pizzuti, Laura, Barchiesi, Giacomo, Sergi, Domenico, Carpano, Silvia, Botti, Claudio, Kayal, Ramy, Sanguineti, Giuseppe, Marchetti, Paolo, Botticelli, Andrea, Marinelli, Daniele, Gamucci, Teresa, Natoli, Clara, Grassadonia, Antonino, Tinari, Nicola, Tomao, Silverio, Tonini, Giuseppe, Santini, Daniele, Michelotti, Aandrea, Mentuccia, Lucia, Vaccaro, Aangela, Magnolfi, Emanuela, Gelibter, Alain, Magri, Valentina, Cortesi, Enrico, D'Onofrio, Loretta, Cassano, Alessandra, Cazzaniga, Marina, Moscetti, Luca, Fabbri, Agnese, Scinto, Angelo Fedele, Corsi, Domenico, Carbognin, Luisa, Bria, Emilio, La Verde, Nicla, Garufi, Carlo, Di Stefano, Pia, Mirabelli, Rossana, Veltri, Enzo, Paris, Ida, Giotta, Francesco, Lorusso, Vito, Landucci, Elisa, Ficorella, Corrado, Roselli, Mario, Adamo, Vincenzo, Ricciardi, Giuseppina, Russo, Antonio, Valerio, Maria Rosaria, Berardi, Rossana, Pistelli, Mirco, Cannita, Katia, Zamagni, Claudio, Garrone, Ornella, Baldini, Editta, Livi, Lorenzo, Meattini, Icro, Del Medico, Pietro, Generali, Daniele, De Maria, Ruggero, Risi, Emanuela, Ciliberto, Gennaro, Villa, Alice, Sperduti, Isabella, Mazzotta, Marco, Barba, Maddalena, Giordano, Antonio, and Vici, Patrizia

Abstract

Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5–24.9, 25–29.9, and 30.0–34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p =.15), while BMI ≥ 30 was associated with worse OS (p =.003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p =.001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p =.03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile.

Published
2020

41. Loss of HER2 and decreased T-DM1 efficacy in HER2 positive advanced breast cancer treated with dual HER2 blockade: the SePHER Study

Author

Bon, G., Pizzuti, L., Laquintana, V., Loria, R., Porru, M., Marchio, C., Krasniqi, E., Barba, M., Maugeri-Sacca, M., Gamucci, T., Berardi, R., Livi, L., Ficorella, C., Natoli, C., Cortesi, E., Generali, D., La Verde, N., Cassano, Alessandra, Bria, Emilio, Moscetti, L., Michelotti, A., Adamo, V., Zamagni, C., Tonini, G., Barchiesi, G., Mazzotta, M., Marinelli, D., Tomao, S., Marchetti, P., Valerio, M. R., Mirabelli, R., Russo, A., Fabbri, M. A., D'Ostilio, N., Veltri, E., Corsi, D., Garrone, O., Paris, I., Sarobba, G., Giotta, F., Garufi, C., Cazzaniga, M., Del Medico, P., Roselli, M., Sanguineti, G., Sperduti, I., Sapino, A., De Maria Marchiano, Ruggero, Leonetti, C., Di Leo, A., Ciliberto, G., Falcioni, R., Vici, P., Cassano A. (ORCID:0000-0002-3311-7163), Bria E. (ORCID:0000-0002-2333-704X), De Maria R. (ORCID:0000-0003-2255-0583), Bon, G., Pizzuti, L., Laquintana, V., Loria, R., Porru, M., Marchio, C., Krasniqi, E., Barba, M., Maugeri-Sacca, M., Gamucci, T., Berardi, R., Livi, L., Ficorella, C., Natoli, C., Cortesi, E., Generali, D., La Verde, N., Cassano, Alessandra, Bria, Emilio, Moscetti, L., Michelotti, A., Adamo, V., Zamagni, C., Tonini, G., Barchiesi, G., Mazzotta, M., Marinelli, D., Tomao, S., Marchetti, P., Valerio, M. R., Mirabelli, R., Russo, A., Fabbri, M. A., D'Ostilio, N., Veltri, E., Corsi, D., Garrone, O., Paris, I., Sarobba, G., Giotta, F., Garufi, C., Cazzaniga, M., Del Medico, P., Roselli, M., Sanguineti, G., Sperduti, I., Sapino, A., De Maria Marchiano, Ruggero, Leonetti, C., Di Leo, A., Ciliberto, G., Falcioni, R., Vici, P., Cassano A. (ORCID:0000-0002-3311-7163), Bria E. (ORCID:0000-0002-2333-704X), and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

Background: HER2-targeting agents have dramatically changed the therapeutic landscape of HER2+ advanced breast cancer (ABC). Within a short time frame, the rapid introduction of new therapeutics has led to the approval of pertuzumab combined with trastuzumab and a taxane in first-line, and trastuzumab emtansine (T-DM1) in second-line. Thereby, evidence of T-DM1 efficacy following trastuzumab/pertuzumab combination is limited, with data from some retrospective reports suggesting lower activity. The purpose of the present study is to investigate T-DM1 efficacy in pertuzumab-pretreated and pertuzumab naïve HER2 positive ABC patients. We also aimed to provide evidence on the exposure to different drugs sequences including pertuzumab and T-DM1 in HER2 positive cell lines. Methods: The biology of HER2 was investigated in vitro through sequential exposure of resistant HER2 + breast cancer cell lines to trastuzumab, pertuzumab, and their combination. In vitro experiments were paralleled by the analysis of data from 555 HER2 + ABC patients treated with T-DM1 and evaluation of T-DM1 efficacy in the 371 patients who received it in second line. Survival estimates were graphically displayed in Kaplan Meier curves, compared by log rank test and, when possibile, confirmed in multivariate models. Results: We herein show evidence of lower activity of T-DM1 in two HER2+ breast cancer cell lines resistant to trastuzumab+pertuzumab, as compared to trastuzumab-resistant cells. Lower T-DM1 efficacy was associated with a marked reduction of HER2 expression on the cell membrane and its nuclear translocation. HER2 downregulation at the membrane level was confirmed in biopsies of four trastuzumab/pertuzumab-pretreated patients. Among the 371 patients treated with second-line T-DM1, median overall survival (mOS) from diagnosis of advanced disease and median progression-free survival to second-line treatment (mPFS2) were 52 and 6 months in 177 patients who received trastuzumab/pertuzumab in f

Published
2020

42. Impact of BMI on HER2+ metastatic breast cancer patients treated with pertuzumab and/or trastuzumab emtansine. Real-world evidence

Author

Krasniqi, E., Pizzuti, L., Barchiesi, G., Sergi, D., Carpano, S., Botti, C., Kayal, R., Sanguineti, G., Marchetti, P., Botticelli, A., Marinelli, D., Gamucci, T., Natoli, C., Grassadonia, A., Tinari, N., Tomao, S., Tonini, Gerolamo, Santini, D., Michelotti, A., Mentuccia, L., Vaccaro, Ascanio Giuseppe, Magnolfi, E., Gelibter, A., Magri, V., Cortesi, E., D'Onofrio, L., Cassano, A., Cazzaniga, M., Moscetti, L., Fabbri, A., Scinto, A. F., Corsi, Domenico Cristiano, Carbognin, L., Bria, Emilio, La Verde, N., Garufi, C., Di Stefano, P., Mirabelli, R., Veltri, E., Paris, Ida, Giotta, F., Lorusso, V., Landucci, E., Ficorella, C., Roselli, M., Adamo, V., Ricciardi, Walter, Russo, A., Valerio, M. R., Berardi, R., Pistelli, M., Cannita, K., Zamagni, C., Garrone, O., Baldini, E., Livi, L., Meattini, I., Del Medico, P., Generali, Daniele, De Maria Marchiano, Ruggero, Risi, E., Ciliberto, G., Villa, Angela Ida, Sperduti, I., Mazzotta, M., Barba, M., Giordano, Alessandro, Vici, P., Tonini G., Vaccaro A., Corsi D., Bria E. (ORCID:0000-0002-2333-704X), Paris I., Ricciardi G. (ORCID:0000-0002-5655-688X), Generali D. (ORCID:0000-0003-2480-3855), De Maria R. (ORCID:0000-0003-2255-0583), Villa A. (ORCID:0000-0003-0679-334X), Giordano A. (ORCID:0000-0002-6978-0880), Krasniqi, E., Pizzuti, L., Barchiesi, G., Sergi, D., Carpano, S., Botti, C., Kayal, R., Sanguineti, G., Marchetti, P., Botticelli, A., Marinelli, D., Gamucci, T., Natoli, C., Grassadonia, A., Tinari, N., Tomao, S., Tonini, Gerolamo, Santini, D., Michelotti, A., Mentuccia, L., Vaccaro, Ascanio Giuseppe, Magnolfi, E., Gelibter, A., Magri, V., Cortesi, E., D'Onofrio, L., Cassano, A., Cazzaniga, M., Moscetti, L., Fabbri, A., Scinto, A. F., Corsi, Domenico Cristiano, Carbognin, L., Bria, Emilio, La Verde, N., Garufi, C., Di Stefano, P., Mirabelli, R., Veltri, E., Paris, Ida, Giotta, F., Lorusso, V., Landucci, E., Ficorella, C., Roselli, M., Adamo, V., Ricciardi, Walter, Russo, A., Valerio, M. R., Berardi, R., Pistelli, M., Cannita, K., Zamagni, C., Garrone, O., Baldini, E., Livi, L., Meattini, I., Del Medico, P., Generali, Daniele, De Maria Marchiano, Ruggero, Risi, E., Ciliberto, G., Villa, Angela Ida, Sperduti, I., Mazzotta, M., Barba, M., Giordano, Alessandro, Vici, P., Tonini G., Vaccaro A., Corsi D., Bria E. (ORCID:0000-0002-2333-704X), Paris I., Ricciardi G. (ORCID:0000-0002-5655-688X), Generali D. (ORCID:0000-0003-2480-3855), De Maria R. (ORCID:0000-0003-2255-0583), Villa A. (ORCID:0000-0003-0679-334X), and Giordano A. (ORCID:0000-0002-6978-0880)

Abstract

Body mass index (BMI) is a main indicator of obesity and its association with breast cancer is well established. However, little is known in the metastatic setting, especially in HER2-positive patients. We assessed the influence of BMI on clinical outcomes of patients treated with pertuzumab and/or trastuzumab emtansine (T-DM1) for HER2+ metastatic breast cancer (mBC). BMI was addressed as a categorical variable, being classified on the basis of the following ranges, that is, 18.5–24.9, 25–29.9, and 30.0–34.9, namely, normal weight, overweight, and Class I obesity. The outcomes chosen were progression-free survival to first-line chemotherapy (PFS1) and overall survival (OS). Overall (N = 709), no impact of BMI was observed on PFS1 (p =.15), while BMI ≥ 30 was associated with worse OS (p =.003). In subjects who progressed to first line (N = 575), analyzing data across PFS1 quartiles and strata of disease burden, BMI predicted lower PFS1 in patients within the I PFS1 quartile and with the lowest disease burden (p =.001). Univariate analysis showed a detrimental effect of BMI ≥ 30 on OS for women within the I PFS1 quartile (p =.03). Results were confirmed in multivariate analysis. According to PFS1 quartiles a higher percentage of patients with high BMI and low disease burden progressed within 6 months of therapy. The effect of BMI on prognosis was also confirmed in multivariate analysis of OS for overall population. In our cohort, a BMI ≥ 30 correlated with worse OS in patients with HER2+ mBC who received pertuzumab and/or T-DM1 but had no impact on PFS to first line. BMI predicted worse I PFS1 quartile.

Published
2020

43. Distinct HR expression patterns significantly affect the clinical behavior of metastatic HER2+ breast cancer and degree of benefit from novel anti-HER2 agents in the real world setting

Author

Pizzuti, L., Krasniqi, E., Barchiesi, G., Della Giulia, M., Izzo, F., Sanguineti, G., Marchetti, P., Mazzotta, M., Giusti, R., Botticelli, A., Gamucci, T., Natoli, C., Grassadonia, A., Tinari, N., Iezzi, L., Tomao, S., Tomao, F., Tonini, G., Santini, D., Astone, Antonio, Michelotti, A., De Angelis, C., Mentuccia, L., Vaccaro, A., Magnolfi, E., Gelibter, A., Magri, V., Cortesi, E., D'Onofrio, L., Cassano, A., Rossi, E., Cazzaniga, M., Moscetti, L., Omarini, C., Piacentini, F., Fabbri, M. A., Scinto, A. F., Corsi, D., Carbognin, L., Bria, Emilio, La Verde, N., Samaritani, R., Garufi, C., Barni, S., Mirabelli, R., Sarmiento, R., Veltri, E. M., D'Auria, G., Paris, I., Giotta, F., Lorusso, V., Cardillo, F., Landucci, E., Mauri, M., Ficorella, C., Roselli, M., Adamo, V., Ricciardi, G. R. R., Russo, A., Berardi, R., Pistelli, M., Fiorio, E., Cannita, K., Sini, V., D'Ostilio, N., Foglietta, J., Greco, F., Zamagni, C., Garrone, O., Di Cocco, B., Baldini, E., Livi, L., Desideri, I., Meattini, I., Sarobba, G., Del Medico, P., De Tursi, M., Generali, D., De Maria Marchiano, Ruggero, Risi, E., Ciliberto, G., Sperduti, I., Villa, A., Barba, M., Di Leo, A., Vici, P., Astone A. (ORCID:0000-0001-9572-309X), Bria E. (ORCID:0000-0002-2333-704X), De Maria R. (ORCID:0000-0003-2255-0583), Pizzuti, L., Krasniqi, E., Barchiesi, G., Della Giulia, M., Izzo, F., Sanguineti, G., Marchetti, P., Mazzotta, M., Giusti, R., Botticelli, A., Gamucci, T., Natoli, C., Grassadonia, A., Tinari, N., Iezzi, L., Tomao, S., Tomao, F., Tonini, G., Santini, D., Astone, Antonio, Michelotti, A., De Angelis, C., Mentuccia, L., Vaccaro, A., Magnolfi, E., Gelibter, A., Magri, V., Cortesi, E., D'Onofrio, L., Cassano, A., Rossi, E., Cazzaniga, M., Moscetti, L., Omarini, C., Piacentini, F., Fabbri, M. A., Scinto, A. F., Corsi, D., Carbognin, L., Bria, Emilio, La Verde, N., Samaritani, R., Garufi, C., Barni, S., Mirabelli, R., Sarmiento, R., Veltri, E. M., D'Auria, G., Paris, I., Giotta, F., Lorusso, V., Cardillo, F., Landucci, E., Mauri, M., Ficorella, C., Roselli, M., Adamo, V., Ricciardi, G. R. R., Russo, A., Berardi, R., Pistelli, M., Fiorio, E., Cannita, K., Sini, V., D'Ostilio, N., Foglietta, J., Greco, F., Zamagni, C., Garrone, O., Di Cocco, B., Baldini, E., Livi, L., Desideri, I., Meattini, I., Sarobba, G., Del Medico, P., De Tursi, M., Generali, D., De Maria Marchiano, Ruggero, Risi, E., Ciliberto, G., Sperduti, I., Villa, A., Barba, M., Di Leo, A., Vici, P., Astone A. (ORCID:0000-0001-9572-309X), Bria E. (ORCID:0000-0002-2333-704X), and De Maria R. (ORCID:0000-0003-2255-0583)

Abstract

We analyzed data from 738 HER2-positive metastatic breast cancer (mbc) patients treated with pertuzumab-based regimens and/or T-DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression-free survival at first-line (mPFS1) was 12 months. Pertuzumab as first-line conferred longer mPFS1 compared to other first-line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second-line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T-DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs-negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T-DM1 in second-line after pertuzumab were significantly lower compared to pertuzumab-naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment-related outcomes of HER2-positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2-positive (mbc) patients.

Published
2020

44. Efficacy and safety of Everolimus and Exemestane in hormone-receptor positive (HR+) human-epidermal-growth-factor negative (HER2−) advanced breast cancer patients: New insights beyond clinical trials. The EVA study

Author

Cicchiello, F, Riva, F, Cazzaniga, M, Pedani, F, Nicolini, M, Butti, C, Liscia, N, Pogliani, C, Capri, G, Alu, M, Febbraro, A, Petrucelli, L, D'Onofrio, L, De Laurentiis, M, Pellegrini, D, Mentuccia, L, Cocciolone, V, Miraglio, E, Bajardi, E, Dester, M, Paterno, E, Guaitoli, G, Ferrarini, I, Gervasi, E, Licata, L, Benedetto, C, Andreis, D, Bordin, E, Ancona, C, Pizzuti, L, Fotia, V, Berardi, R, Airoldi, M, Arcangeli, V, Artale, S, Atzori, F, Ballerio, A, Bianchi, G, Blasi, L, Campidoglio, S, Ciccarese, M, Cursano, M, Piezzo, M, Fabi, A, Ferrari, L, Ferzi, A, Ficorella, C, Frassoldati, A, Fumagalli, A, Garrone, O, Gebbia, V, Generali, D, La Verde, N, Maur, M, Michelotti, A, Moretti, G, Musolino, A, Palumbo, R, Pistelli, M, Porpiglia, M, Sartori, D, Scavelli, C, Schirone, A, Turletti, A, Valerio, M, Vici, P, Zambelli, A, Clivio, L, Torri, V, Cicchiello F., Riva F., Cazzaniga M. E., Pedani F., Nicolini M., Butti C., Liscia N., Pogliani C., Capri G., Alu M., Febbraro A., Petrucelli L., D'Onofrio L., De Laurentiis M., Pellegrini D., Mentuccia L., Cocciolone V., Miraglio E., Bajardi E., Dester M., Paterno E., Guaitoli G., Ferrarini I., Gervasi E., Licata L., Benedetto C., Andreis D., Bordin E., Ancona C., Pizzuti L., Fotia V., Berardi R., Airoldi M., Arcangeli V., Artale S., Atzori F., Ballerio A., Bianchi G. V., Blasi L., Campidoglio S., Ciccarese M., Cursano M. C., Piezzo M., Fabi A., Ferrari L., Ferzi A., Ficorella C., Frassoldati A., Fumagalli A., Garrone O., Gebbia V., Generali D., La Verde N., Maur M., Michelotti A., Moretti G., Musolino A., Palumbo R., Pistelli M., Porpiglia M., Sartori D., Scavelli C., Schirone A., Turletti A., Valerio M. R., Vici P., Zambelli A., Clivio L., Torri V., Cicchiello, F, Riva, F, Cazzaniga, M, Pedani, F, Nicolini, M, Butti, C, Liscia, N, Pogliani, C, Capri, G, Alu, M, Febbraro, A, Petrucelli, L, D'Onofrio, L, De Laurentiis, M, Pellegrini, D, Mentuccia, L, Cocciolone, V, Miraglio, E, Bajardi, E, Dester, M, Paterno, E, Guaitoli, G, Ferrarini, I, Gervasi, E, Licata, L, Benedetto, C, Andreis, D, Bordin, E, Ancona, C, Pizzuti, L, Fotia, V, Berardi, R, Airoldi, M, Arcangeli, V, Artale, S, Atzori, F, Ballerio, A, Bianchi, G, Blasi, L, Campidoglio, S, Ciccarese, M, Cursano, M, Piezzo, M, Fabi, A, Ferrari, L, Ferzi, A, Ficorella, C, Frassoldati, A, Fumagalli, A, Garrone, O, Gebbia, V, Generali, D, La Verde, N, Maur, M, Michelotti, A, Moretti, G, Musolino, A, Palumbo, R, Pistelli, M, Porpiglia, M, Sartori, D, Scavelli, C, Schirone, A, Turletti, A, Valerio, M, Vici, P, Zambelli, A, Clivio, L, Torri, V, Cicchiello F., Riva F., Cazzaniga M. E., Pedani F., Nicolini M., Butti C., Liscia N., Pogliani C., Capri G., Alu M., Febbraro A., Petrucelli L., D'Onofrio L., De Laurentiis M., Pellegrini D., Mentuccia L., Cocciolone V., Miraglio E., Bajardi E., Dester M., Paterno E., Guaitoli G., Ferrarini I., Gervasi E., Licata L., Benedetto C., Andreis D., Bordin E., Ancona C., Pizzuti L., Fotia V., Berardi R., Airoldi M., Arcangeli V., Artale S., Atzori F., Ballerio A., Bianchi G. V., Blasi L., Campidoglio S., Ciccarese M., Cursano M. C., Piezzo M., Fabi A., Ferrari L., Ferzi A., Ficorella C., Frassoldati A., Fumagalli A., Garrone O., Gebbia V., Generali D., La Verde N., Maur M., Michelotti A., Moretti G., Musolino A., Palumbo R., Pistelli M., Porpiglia M., Sartori D., Scavelli C., Schirone A., Turletti A., Valerio M. R., Vici P., Zambelli A., Clivio L., and Torri V.

Abstract

Background The BOLERO-2 trial reported efficacy and safety of Everolimus (EVE) and Exemestane (EXE) combination in HR+ advanced breast cancer (ABC) patients. The BALLET trial further evaluated the safety of EVE-EXE in HR+ ABC patients, without reporting efficacy data. Aim of the EVA real-life study was to collect data of efficacy and safety of EVE-EXE combination in the clinical setting, as well as exploring efficacy according to EVE Dose-Intensity (DI) and to previous treatment with Fulvestrant. Patients and methods This study aimed to describe the outcome of ABC pts treated with EVE-EXE combination in terms of median duration of EVE treatment and ORR in a real-life setting. Results From July 2013 to December 2015, the EVA study enrolled 404 pts. Median age was 61 years (33–83). Main metastatic sites were: bone (69.1%), soft tissue (34.7%) and viscera (33.2%). Median number of previous treatments was 2 (1–7). 43.3% of the pts had received Fulvestrant. Median exposure to EVE was 31.0 weeks (15.4–58.3) in the whole population. No difference was observed in terms of EVE exposure duration according to DI (p for trend = 0.27) or type of previous treatments (p = 0.33). ORR and Disease Control Rate (DCR) were observed in 31.6% and 60.7% of the patients, respectively, with the lowest ORRs confined in CHT pre-treated patients or in those who received the lowest DI of EVE. Grade 3-4 adverse events (AEs) were reported in 37.9% of the patients. Main AEs were: stomatitis (11.2%), non-infectious pneumonitis - NIP (3.8%), anaemia (3.8%) and fatigue (3.2%). Conclusions The EVA study provided new insights in the use of EVE-EVE combination in HR+ ABC pts many years after the publication of the pivotal trial. The combination is safe and the best response could be obtained in patients receiving the full dose of EVE and/or after hormone-therapy as Fulvestrant in ABC.

Published
2017

45. Dose intensity and efficacy of the combination of everolimus and exemestane (EVE/EXE) in a real-world population of hormone receptor-positive (ER+/PgR+), HER2-negative advanced breast cancer (ABC) patients: a multicenter Italian experience

Author

Ciccarese, M, Fabi, A, Moscetti, L, Cazzaniga, M, Petrucelli, L, Forcignanò, R, Lupo, L, De Matteis, E, Chiuri, V, Cairo, G, Febbraro, A, Giordano, G, Giampaglia, M, Bilancia, D, La Verde, N, Maiello, E, Morritti, M, Giotta, F, Lorusso, V, Latorre, A, Scavelli, C, Romito, S, Cusmai, A, Palmiotti, G, Surico, Ciccarese M, Fabi A, Moscetti L, Cazzaniga M, Petrucelli L, Forcignanò R, Lupo LI, De Matteis E, Chiuri VE, Cairo G, Febbraro A, Giordano G, Giampaglia M, Bilancia D, La Verde N, Maiello E, Morritti M, Giotta F, Lorusso V, Latorre A, Scavelli C, Romito S, Cusmai A, Palmiotti G, Ciccarese, M, Fabi, A, Moscetti, L, Cazzaniga, M, Petrucelli, L, Forcignanò, R, Lupo, L, De Matteis, E, Chiuri, V, Cairo, G, Febbraro, A, Giordano, G, Giampaglia, M, Bilancia, D, La Verde, N, Maiello, E, Morritti, M, Giotta, F, Lorusso, V, Latorre, A, Scavelli, C, Romito, S, Cusmai, A, Palmiotti, G, Surico, Ciccarese M, Fabi A, Moscetti L, Cazzaniga M, Petrucelli L, Forcignanò R, Lupo LI, De Matteis E, Chiuri VE, Cairo G, Febbraro A, Giordano G, Giampaglia M, Bilancia D, La Verde N, Maiello E, Morritti M, Giotta F, Lorusso V, Latorre A, Scavelli C, Romito S, Cusmai A, and Palmiotti G

Abstract

Aim: This retrospective analysis focused on the effect of treatment with EVE/EXE in a real-world population outside of clinical trials. We examined the efficacy of this combination in terms of PFS and RR related to dose intensity (5 mg daily versus 10 mg daily) and tolerability. Methods: 163 HER2-negative ER+/PgR+ ABC patients, treated with EVE/EXE from May 2011 to March 2016, were included in the analysis. The primary endpoints were the correlation between the daily dose and RR and PFS, as well as an evaluation of the tolerability of the combination. Secondary endpoints were RR, PFS, and OS according to the line of treatment. Patients were classified into three different groups, each with a different dose intensity of everolimus (A, B, C). Results: RR was 29.8% (A), 27.8% (B) (p = 0.953), and not evaluable (C). PFS was 9 months (95% CI 7–11) (A), 10 months (95% CI 9–11) (B), and 5 months (95% CI 2–8) (C), p = 0.956. OS was 38 months (95% CI 24–38) (A), median not reached (B), and 13 months (95% CI 10–25) (C), p = 0.002. Adverse events were stomatitis 57.7% (11.0% grade 3–4), asthenia 46.0% (6.1% grade 3–4), hypercholesterolemia 46.0% (0.6% grade 3–4), and hyperglycemia 35.6% (5.5% grade 3–4). The main reason for discontinuation/interruption was grade 2–3 stomatitis. Conclusions: No correlation was found between dose intensity (5 vs. 10 mg labeled dose) and efficacy in terms of RR and PFS. The tolerability of the higher dose was poor in our experience, although this had no impact on efficacy.

Published
2017

46. NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel plus trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2(+) breast cancer

Author

Jacobs, S, Robidoux, A, Abraham, J, Perez-Garcia, J, La Verde, N, Orcutt, J, Cazzaniga, M, Piette, F, Antolin, S, Aguirre, E, Cortes, J, Llombart-Cussac, A, Di Cosimo, S, Kim, R, Feng, H, Lipchik, C, Lucas, P, Srinivasan, A, Wang, Y, Song, N, Gavin, P, Balousek, A, Paik, S, Allegra, C, Wolmark, N, and Pogue-Geile, K

Subjects
Breast cancer, Neratinib, Neoadjuvant, skin and connective tissue diseases
Abstract

Purpose: The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2(+)) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses. Experimental design: pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A). Pre-treatment biopsies and residual tumors were also compared to identify molecular changes. Results: The numerical pCR rate in the trastuzumab plus neratinib arm (50% [95%CI 34-66%]) was greater than that for single-targeted therapies with trastuzumab (38% [95%CI 24-54]) or neratinib (33% [95%CI 20-50]) in the overall cohort but was not statistically significant. Hormone receptor-negative (HR-) tumors had a higher pCR rate than HR+ tumors in all three treatment arms, with the highest pCR rate in the combination arm. Diarrhea was the most frequent adverse event and occurred in virtually all patients who received neratinib-based therapy. Grade 3 diarrhea was reported in 31% of patients; there were no grade 4 events. Our 8-gene signature, previously validated for trastuzumab benefit in two different clinical trials in the adjuvant setting, was correlated with pCR across all arms of NSABP FB-7. Specifically, patients predicted to receive no trastuzumab benefit had a significantly lower pCR rate than did patients predicted to receive the most benefit (P = 0.03). FCGR genotyping showed that patients who were homozygous for the Fc low-binding phenylalanine (F) allele for FCGR3A-158V/F were less likely to achieve pCR. Conclusions: Combining trastuzumab plus neratinib with paclitaxel increased the absolute pCR rate in the overall cohort and in HR- patients. The 8-gene signature, which is validated for predicting trastuzumab benefit in the adjuvant setting, was associated with pCR in the neoadjuvant setting, but remains to be validated as a predictive marker in a larger neoadjuvant clinical trial. HR status, and the FCGR3A-158V/F genotype, also warrant further investigation to identify HER2(+) patients who may benefit from additional anti-HER2 therapies beyond trastuzumab. All of these markers will require further validation in the neoadjuvant setting.

Published
2019

47. Recommendations for the implementation of BRCA testing in ovarian cancer patients and their relatives

Author

Gori, S, Barberis, M, Bella, M, Buttitta, F, Capoluongo, E, Carrera, P, Colombo, N, Cortesi, L, Genuardi, M, Gion, M, Guarneri, V, Incorvaia, L, La Verde, N, Lorusso, D, Marchetti, A, Marchetti, P, Normanno, N, Pasini, B, Pensabene, M, Pignata, S, Radice, P, Ricevuto, E, Sapino, A, Tagliaferri, P, Tassone, P, Trevisiol, C, Truini, M, Varesco, L, Russo, A, Bella, MA, Pasini B, Gori, S, Barberis, M, Bella, M, Buttitta, F, Capoluongo, E, Carrera, P, Colombo, N, Cortesi, L, Genuardi, M, Gion, M, Guarneri, V, Incorvaia, L, La Verde, N, Lorusso, D, Marchetti, A, Marchetti, P, Normanno, N, Pasini, B, Pensabene, M, Pignata, S, Radice, P, Ricevuto, E, Sapino, A, Tagliaferri, P, Tassone, P, Trevisiol, C, Truini, M, Varesco, L, Russo, A, Bella, MA, and Pasini B

Abstract

The current availability of new Poly(ADP-ribose) Polymerase (PARP)-inhibitors for the treatment of ovarian cancer patients independently of the presence of a BRCA pathogenic variant, together with the validation of somatic test for the analysis of BRCA1/2 genes, involves the need to optimise the guidelines for BRCA testing. The AIOM-SIGU-SIBIOC-SIAPEC-IAP Italian Scientific Societies, in this position paper, recommend the implementation of BRCA testing with 2 main objectives: the first is the identification of ovarian cancer patients with higher probability of benefit from specific anticancer treatments (test for response to therapy); the second goal, through BRCA testing in the family members of ovarian cancer patients, is the identification of carriers of pathogenic variant, who have inheredited predisposition to cancer development (test for cancer risk). These individuals with increased risk of cancer, should be encouraged to participate in dedicated high-risk surveillance clinics and specific risk-reducing measures (primary and/or secondary prevention programs).

Published
2019

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