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1. 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

2. Predictive ability of a drug-based score in patients with advanced non-small-cell lung cancer receiving first-line immunotherapy

Author

Buti, S, Bersanelli, M, Perrone, F, Bracarda, S, Di Maio, M, Giusti, R, Nigro, O, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Ferrara, M, Bria, E, Grossi, F, Bareggi, C, Berardi, R, Torniai, M, Cantini, L, Sforza, V, Genova, C, Chiari, R, Rocco, D, Della Gravara, L, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Citarella, F, Russano, M, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Follador, A, Bisonni, R, Tuzi, A, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Tabbò, F, Olmetto, E, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Addeo, A, Friedlaender, A, Cannita, K, Porzio, G, Ficorella, C, Carmisciano, L, Pinato, D, Mazzaschi, G, Tiseo, M, Cortellini, A, Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R, Nigro O, Cortinovis D, Aerts JGJV, Guaitoli G, Barbieri F, Ferrara MG, Bria E, Grossi F, Bareggi C, Berardi R, Torniai M, Cantini L, Sforza V, Genova C, Chiari R, Rocco D, Della Gravara L, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Citarella F, Russano M, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Follador A, Bisonni R, Tuzi A, Minuti G, Landi L, Ricciardi S, Migliorino MR, Tabbò F, Olmetto E, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Addeo A, Friedlaender A, Cannita K, Porzio G, Ficorella C, Carmisciano L, Pinato DJ, Mazzaschi G, Tiseo M, Cortellini A, Buti, S, Bersanelli, M, Perrone, F, Bracarda, S, Di Maio, M, Giusti, R, Nigro, O, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Ferrara, M, Bria, E, Grossi, F, Bareggi, C, Berardi, R, Torniai, M, Cantini, L, Sforza, V, Genova, C, Chiari, R, Rocco, D, Della Gravara, L, Gori, S, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Citarella, F, Russano, M, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Follador, A, Bisonni, R, Tuzi, A, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Tabbò, F, Olmetto, E, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Addeo, A, Friedlaender, A, Cannita, K, Porzio, G, Ficorella, C, Carmisciano, L, Pinato, D, Mazzaschi, G, Tiseo, M, Cortellini, A, Buti S, Bersanelli M, Perrone F, Bracarda S, Di Maio M, Giusti R, Nigro O, Cortinovis D, Aerts JGJV, Guaitoli G, Barbieri F, Ferrara MG, Bria E, Grossi F, Bareggi C, Berardi R, Torniai M, Cantini L, Sforza V, Genova C, Chiari R, Rocco D, Della Gravara L, Gori S, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Citarella F, Russano M, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Follador A, Bisonni R, Tuzi A, Minuti G, Landi L, Ricciardi S, Migliorino MR, Tabbò F, Olmetto E, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Addeo A, Friedlaender A, Cannita K, Porzio G, Ficorella C, Carmisciano L, Pinato DJ, Mazzaschi G, Tiseo M, and Cortellini A

Abstract

Background: We previously demonstrated the cumulative poor prognostic role of concomitant medications on the clinical outcome of patients with advanced cancer treated with immune checkpoint inhibitors, creating and validating a drug-based prognostic score to be calculated before immunotherapy initiation in patients with advanced solid tumours. This ‘drug score’ was calculated assigning score 1 for each between proton-pump inhibitor and antibiotic administration until a month before cancer therapy initiation and score 2 in case of corticosteroid intake. The good risk group included patients with score 0, intermediate risk with score 1–2 and poor risk with score 3–4. Methods: Aiming at validating the prognostic and putative predictive ability depending on the anticancer therapy, we performed the present comparative analysis in two cohorts of advanced non–small-cell lung cancer (NSCLC), respectively, receiving first-line pembrolizumab or chemotherapy through a random case-control matching and through a pooled multivariable analysis including the interaction between the computed score and the therapeutic modality (pembrolizumab vs chemotherapy). Results: Nine hundred fifty and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. After the case-control random matching, 589 patients from the pembrolizumab cohort and 589 from the chemotherapy cohort were paired, with no statistically significant differences between the characteristics of the matched subjects. Among the pembrolizumab-treated group, good, intermediate and poor risk evaluable patients achieved an objective response rate (ORR) of 50.0%, 37.7% and 23.4%, respectively, (p < 0.0001), whereas among the chemotherapy-treated group, patients achieved an ORR of 37.0%, 40.0% and 32.4%, respectively (p = 0.4346). The median progression-free survival (PFS) of good, intermediate and poor risk groups was 13.9 months, 6.3 months and 2.8 months, respectively, within the pembrolizumab coh

Published
2021

3. Differential influence of antibiotic therapy and other medications on oncological outcomes of patients with non-small cell lung cancer treated with first-line pembrolizumab versus cytotoxic chemotherapy

Author

Cortellini, A, Di Maio, M, Nigro, O, Leonetti, A, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Giusti, R, Ferrara, M, Bria, E, D'Argento, E, Grossi, F, Rijavec, E, Guida, A, Berardi, R, Torniai, M, Sforza, V, Genova, C, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Della Gravara, L, Inno, A, Michele, T, Grassadonia, A, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Santini, D, Citarella, F, Russano, M, Cantini, L, Tuzi, A, Bordi, P, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Passiglia, F, Bironzo, P, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Friedlaender, A, Addeo, A, Cannita, K, Ficorella, C, Porzio, G, Pinato, D, Cortellini A, Di Maio M, Nigro O, Leonetti A, Cortinovis D, Aerts JG, Guaitoli G, Barbieri F, Giusti R, Ferrara MG, Bria E, D'Argento E, Grossi F, Rijavec E, Guida A, Berardi R, Torniai M, Sforza V, Genova C, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Della Gravara L, Inno A, Michele T, Grassadonia A, Di Marino P, Mansueto G, Zoratto F, Filetti M, Santini D, Citarella F, Russano M, Cantini L, Tuzi A, Bordi P, Minuti G, Landi L, Ricciardi S, Migliorino MR, Passiglia F, Bironzo P, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Friedlaender A, Addeo A, Cannita K, Ficorella C, Porzio G, Pinato DJ, Cortellini, A, Di Maio, M, Nigro, O, Leonetti, A, Cortinovis, D, Aerts, J, Guaitoli, G, Barbieri, F, Giusti, R, Ferrara, M, Bria, E, D'Argento, E, Grossi, F, Rijavec, E, Guida, A, Berardi, R, Torniai, M, Sforza, V, Genova, C, Mazzoni, F, Garassino, M, De Toma, A, Signorelli, D, Gelibter, A, Siringo, M, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Della Gravara, L, Inno, A, Michele, T, Grassadonia, A, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Santini, D, Citarella, F, Russano, M, Cantini, L, Tuzi, A, Bordi, P, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Passiglia, F, Bironzo, P, Metro, G, Adamo, V, Russo, A, Spinelli, G, Banna, G, Friedlaender, A, Addeo, A, Cannita, K, Ficorella, C, Porzio, G, Pinato, D, Cortellini A, Di Maio M, Nigro O, Leonetti A, Cortinovis D, Aerts JG, Guaitoli G, Barbieri F, Giusti R, Ferrara MG, Bria E, D'Argento E, Grossi F, Rijavec E, Guida A, Berardi R, Torniai M, Sforza V, Genova C, Mazzoni F, Garassino MC, De Toma A, Signorelli D, Gelibter A, Siringo M, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Della Gravara L, Inno A, Michele T, Grassadonia A, Di Marino P, Mansueto G, Zoratto F, Filetti M, Santini D, Citarella F, Russano M, Cantini L, Tuzi A, Bordi P, Minuti G, Landi L, Ricciardi S, Migliorino MR, Passiglia F, Bironzo P, Metro G, Adamo V, Russo A, Spinelli GP, Banna GL, Friedlaender A, Addeo A, Cannita K, Ficorella C, Porzio G, and Pinato DJ

Abstract

Background Some concomitant medications including antibiotics (ATB) have been reproducibly associated with worse survival following immune checkpoint inhibitors (ICIs) in unselected patients with non-small cell lung cancer (NSCLC) (according to programmed death-ligand 1 (PD-L1) expression and treatment line). Whether such relationship is causative or associative is matter of debate. Methods We present the outcomes analysis according to concomitant baseline medications (prior to ICI initiation) with putative immune-modulatory effects in a large cohort of patients with metastatic NSCLC with a PD-L1 expression >= 50%, receiving first-line pembrolizumab monotherapy. We also evaluated a control cohort of patients with metastatic NSCLC treated with first-line chemotherapy. The interaction between key medications and therapeutic modality (pembrolizumab vs chemotherapy) was validated in pooled multivariable analyses. Results 950 and 595 patients were included in the pembrolizumab and chemotherapy cohorts, respectively. Corticosteroid and proton pump inhibitor (PPI) therapy but not ATB therapy was associated with poorer performance status at baseline in both the cohorts. No association with clinical outcomes was found according to baseline statin, aspirin, beta-blocker and metformin within the pembrolizumab cohort. On the multivariable analysis, ATB emerged as a strong predictor of worse overall survival (OS) (HR=1.42 (95% CI 1.13 to 1.79); p=0.0024), and progression free survival (PFS) (HR=1.29 (95% CI 1.04 to 1.59); p=0.0192) in the pembrolizumab but not in the chemotherapy cohort. Corticosteroids were associated with shorter PFS (HR=1.69 (95% CI 1.42 to 2.03); p<0.0001), and OS (HR=1.93 (95% CI 1.59 to 2.35); p<0.0001) following pembrolizumab, and shorter PFS (HR=1.30 (95% CI 1.08 to 1.56), p=0.0046) and OS (HR=1.58 (95% CI 1.29 to 1.94), p<0.0001), following chemotherapy. PPIs were associated with worse OS (HR=1.49 (95% CI 1.26 to 1.77); p<0.0001) with pem

Published
2021

4. Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case-control matched analysis from a large multicenter study

Author

Cortellini, A, De Giglio, A, Cannita, K, Cortinovis, D, Cornelissen, R, Baldessari, C, Giusti, R, D'Argento, E, Grossi, F, Santoni, M, Catino, A, Berardi, R, Sforza, V, Rossi, G, Antonuzzo, L, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, M, Follador, A, Rastelli, F, Chiari, R, Gravara, L, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Pensieri, M, Russano, M, Cantini, L, Nigro, O, Leonetti, A, Bordi, P, Minuti, G, Landi, L, De Toma, A, Donisi, C, Ricciardi, S, Migliorino, M, Napoli, V, Leone, G, Metro, G, Banna, G, Friedlaender, A, Addeo, A, Ficorella, C, Porzio, G, Cortellini A, De Giglio A, Cannita K, Cortinovis D, Cornelissen R, Baldessari C, Giusti R, D'Argento E, Grossi F, Santoni M, Catino A, Berardi R, Sforza V, Rossi G, Antonuzzo L, Di Noia V, Signorelli D, Gelibter A, Occhipinti MA, Follador A, Rastelli F, Chiari R, Gravara LD, Inno A, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Pensieri MV, Russano M, Cantini L, Nigro O, Leonetti A, Bordi P, Minuti G, Landi L, De Toma A, Donisi C, Ricciardi S, Migliorino MR, Napoli VM, Leone G, Metro G, Banna GL, Friedlaender A, Addeo A, Ficorella C, Porzio G, Cortellini, A, De Giglio, A, Cannita, K, Cortinovis, D, Cornelissen, R, Baldessari, C, Giusti, R, D'Argento, E, Grossi, F, Santoni, M, Catino, A, Berardi, R, Sforza, V, Rossi, G, Antonuzzo, L, Di Noia, V, Signorelli, D, Gelibter, A, Occhipinti, M, Follador, A, Rastelli, F, Chiari, R, Gravara, L, Inno, A, De Tursi, M, Di Marino, P, Mansueto, G, Zoratto, F, Filetti, M, Montrone, M, Citarella, F, Pensieri, M, Russano, M, Cantini, L, Nigro, O, Leonetti, A, Bordi, P, Minuti, G, Landi, L, De Toma, A, Donisi, C, Ricciardi, S, Migliorino, M, Napoli, V, Leone, G, Metro, G, Banna, G, Friedlaender, A, Addeo, A, Ficorella, C, Porzio, G, Cortellini A, De Giglio A, Cannita K, Cortinovis D, Cornelissen R, Baldessari C, Giusti R, D'Argento E, Grossi F, Santoni M, Catino A, Berardi R, Sforza V, Rossi G, Antonuzzo L, Di Noia V, Signorelli D, Gelibter A, Occhipinti MA, Follador A, Rastelli F, Chiari R, Gravara LD, Inno A, De Tursi M, Di Marino P, Mansueto G, Zoratto F, Filetti M, Montrone M, Citarella F, Pensieri MV, Russano M, Cantini L, Nigro O, Leonetti A, Bordi P, Minuti G, Landi L, De Toma A, Donisi C, Ricciardi S, Migliorino MR, Napoli VM, Leone G, Metro G, Banna GL, Friedlaender A, Addeo A, Ficorella C, and Porzio G

Abstract

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking stat

Published
2021

5. Post-progression outcomes of NSCLC patients with PD-L1 expression ≥ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study

Author

Cortellini, A, Cannita, K, Tiseo, M, Cortinovis, D, Aerts, J, Baldessari, C, Giusti, R, Ferrara, M, D'Argento, E, Grossi, F, Guida, A, Berardi, R, Morabito, A, Genova, C, Antonuzzo, L, Mazzoni, F, De Toma, A, Signorelli, D, Gelibter, A, Targato, G, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Filetti, M, Bracarda, S, Citarella, F, Russano, M, Cantini, L, Nigro, O, Buti, S, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Natalizio, S, Simona, C, De Filippis, M, Metro, G, Adamo, V, Russo, A, Spinelli, G, Di Maio, M, Banna, G, Friedlaender, A, Addeo, A, Pinato, D, Ficorella, C, Porzio, G, Cortellini A, Cannita K, Tiseo M, Cortinovis D, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, Porzio G, Cortellini, A, Cannita, K, Tiseo, M, Cortinovis, D, Aerts, J, Baldessari, C, Giusti, R, Ferrara, M, D'Argento, E, Grossi, F, Guida, A, Berardi, R, Morabito, A, Genova, C, Antonuzzo, L, Mazzoni, F, De Toma, A, Signorelli, D, Gelibter, A, Targato, G, Rastelli, F, Chiari, R, Rocco, D, Gori, S, De Tursi, M, Mansueto, G, Zoratto, F, Filetti, M, Bracarda, S, Citarella, F, Russano, M, Cantini, L, Nigro, O, Buti, S, Minuti, G, Landi, L, Ricciardi, S, Migliorino, M, Natalizio, S, Simona, C, De Filippis, M, Metro, G, Adamo, V, Russo, A, Spinelli, G, Di Maio, M, Banna, G, Friedlaender, A, Addeo, A, Pinato, D, Ficorella, C, Porzio, G, Cortellini A, Cannita K, Tiseo M, Cortinovis D, Aerts JGJV, Baldessari C, Giusti R, Ferrara MG, D'Argento E, Grossi F, Guida A, Berardi R, Morabito A, Genova C, Antonuzzo L, Mazzoni F, De Toma A, Signorelli D, Gelibter A, Targato G, Rastelli F, Chiari R, Rocco D, Gori S, De Tursi M, Mansueto G, Zoratto F, Filetti M, Bracarda S, Citarella F, Russano M, Cantini L, Nigro O, Buti S, Minuti G, Landi L, Ricciardi S, Migliorino MR, Natalizio S, Simona C, De Filippis M, Metro G, Adamo V, Russo A, Spinelli GP, Di Maio M, Banna GL, Friedlaender A, Addeo A, Pinato DJ, Ficorella C, and Porzio G

Abstract

Background: Treatment sequencing with first-line immunotherapy, followed by second-line chemotherapy, is still a viable option for NSCLC patients with PD-L1 expression ≥50%. Methods: We evaluated post-progression treatment pathways in a large real-world cohort of metastatic NSCLC patients with PD-L1 expression ≥ 50% treated with first-line pembrolizumab monotherapy. Results: Overall, 974 patients were included. With a median follow-up of 22.7 months (95%CI: 21.6–38.2), the median overall survival (OS) of the entire population was 15.8 months (95%CI: 13.5–17.5; 548 events). At the data cutoff, among the 678 patients who experienced disease progression, 379 (55.9%) had not received any further treatment, and 359 patients (52.9%) had died. Patients who did not receive post-progression therapies were older (p = 0.0011), with a worse ECOG-PS (p < 0.0001) and were on corticosteroids prior to pembrolizumab (p = 0.0024). At disease progression, 198 patients (29.2%) received a switched approach and 101 (14.9%) received pembrolizumab ByPD either alone (64 [9.4%]) or in combination with local ablative treatments (37 [5.5%]) (LATs). After a random-case control matching according to ECOG-PS, CNS metastases, bone metastases, and (previous) best response to pembrolizumab, patients receiving pembrolizumab ByPD plus LATs were confirmed to have a significantly longer post-progression OS compared to patients receiving pembrolizumab ByPD alone 13.9 months versus 7.8 months (p = 0.0179) 241 patients (35.5%) among the 678 who had experienced PD, received a second-line systemic treatment (regardless of previous treatment beyond PD). As compared to first-line treatment commencement, patients’ features at the moment of second-line initiation showed a significantly higher proportion of patients aged under 70 years (p = 0.0244), with a poorer ECOG-PS (p < 0.0001) and having CNS (p = 0.0001), bone (p = 0.0266) and liver metastases (p = 0.0148). Conclusions: In the real-world scenario NSC

Published
2021

7. Osimertinib beyond disease progression in T790M EGFR-positive NSCLC patients: a multicenter study of clinicians' attitudes

Author

Cortellini, A, Leonetti, A, Catino, A, Pizzutillo, P, Ricciuti, B, De Giglio, A, Chiari, R, Bordi, P, Santini, D, Giusti, R, De Tursi, M, Brocco, D, Zoratto, F, Rastelli, F, Citarella, F, Russano, M, Filetti, M, Marchetti, P, Berardi, R, Torniai, M, Cortinovis, D, Sala, E, Maggioni, C, Follador, A, Macerelli, M, Nigro, O, Tuzi, A, Iacono, D, Migliorino, M, Banna, G, Porzio, G, Cannita, K, Ferrara, M, Bria, E, Galetta, D, Ficorella, C, Tiseo, M, Cortellini A, Leonetti A, Catino A, Pizzutillo P, Ricciuti B, De Giglio A, Chiari R, Bordi P, Santini D, Giusti R, De Tursi M, Brocco D, Zoratto F, Rastelli F, Citarella F, Russano M, Filetti M, Marchetti P, Berardi R, Torniai M, Cortinovis D, Sala E, Maggioni C, Follador A, Macerelli M, Nigro O, Tuzi A, Iacono D, Migliorino MR, Banna G, Porzio G, Cannita K, Ferrara MG, Bria E, Galetta D, Ficorella C, Tiseo M., Cortellini, A, Leonetti, A, Catino, A, Pizzutillo, P, Ricciuti, B, De Giglio, A, Chiari, R, Bordi, P, Santini, D, Giusti, R, De Tursi, M, Brocco, D, Zoratto, F, Rastelli, F, Citarella, F, Russano, M, Filetti, M, Marchetti, P, Berardi, R, Torniai, M, Cortinovis, D, Sala, E, Maggioni, C, Follador, A, Macerelli, M, Nigro, O, Tuzi, A, Iacono, D, Migliorino, M, Banna, G, Porzio, G, Cannita, K, Ferrara, M, Bria, E, Galetta, D, Ficorella, C, Tiseo, M, Cortellini A, Leonetti A, Catino A, Pizzutillo P, Ricciuti B, De Giglio A, Chiari R, Bordi P, Santini D, Giusti R, De Tursi M, Brocco D, Zoratto F, Rastelli F, Citarella F, Russano M, Filetti M, Marchetti P, Berardi R, Torniai M, Cortinovis D, Sala E, Maggioni C, Follador A, Macerelli M, Nigro O, Tuzi A, Iacono D, Migliorino MR, Banna G, Porzio G, Cannita K, Ferrara MG, Bria E, Galetta D, Ficorella C, and Tiseo M.

Abstract

Background: In most cases, T790M EGFR-positive NSCLC patients receiving osimertinib developed “non-drugable” progression, as the patients with common EGFR-sensitizing mutations were treated with first-line osimertinib. In both settings, chemotherapy represents the standard treatment and local ablative treatments (LATs) are potential useful options in the case of oligo-progression. Methods: We conducted a study on “post-progression” (pp) outcomes of T790M EGFR-positive NSCLC patients treated with osimertinib, according to the therapeutic strategy applied: osimertinib beyond progression (± LATs), “switched therapies” or best supportive care only (BSC). Results: 144 consecutive patients were evaluated: 53 (36.8%) did not received post-progression treatments (BSC), while 91 (63.2%) patients received at least 1 subsequent treatment; 50 patients (54.9%) received osimertinib beyond disease progression [19 (20.9%) of them with adjunctive LATs] and 41 (45.1%) a switched therapy. Median ppPFS (progression-free survival) and median ppOS (overall survival) of patients who received osimertinib beyond progression vs. switched therapies were 6.4 months vs. 4.7 months, respectively [HR 0.57 (95% CI 0.35–0.92), p = 0.0239] and 11.3 months vs 7.8 months, respectively [HR 0.57 (95% CI 0.33–0.98), p = 0.0446]. Among patients who received osimertinib beyond progression with and without LATs median ppPFS was 6.4 months and 5.7 months, respectively [HR 0.90 (95% CI 0.68–1.18), p = 0.4560], while median ppOS was 20.2 months and 9.9 months, respectively [HR 0.73 (95% CI 0.52–1.03), p = 0.0748]. At the univariate analysis, the only factor significantly related to the ppPFS was the therapeutic strategy in favor of osimertinib beyond progression (± LATs). Moreover, the only variable which was significantly related to ppOS at the multivariate analysis was osimertinib beyond progression (± LATs). Conclusion: Our study confirmed that in clinical practice, in case of “non-druggable” disease progre

Published
2020

8. Immune-related Adverse Events of Pembrolizumab in a Large Real-world Cohort of Patients With NSCLC With a PD-L1 Expression ≥ 50% and Their Relationship With Clinical Outcomes

Author

Cortellini, A, Friedlaender, A, Banna, G, Porzio, G, Bersanelli, M, Cappuzzo, F, Aerts, J, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Berardi, R, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, Di Marino, P, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Ghidini, M, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Occhipinti, M, Citarella, F, Marco, R, Torniai, M, Cantini, L, Follador, A, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Leonetti, A, Pettoruti, L, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Bertolini, F, Della Gravara, L, Dal Bello, M, Belderbos, R, De Filippis, M, Cecchi, C, Ricciardi, S, Donisi, C, De Toma, A, Proto, C, Addeo, A, Cantale, O, Ricciuti, B, Genova, C, Morabito, A, Santini, D, Ficorella, C, Cannita, K, Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Marco R, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, Cannita K., Cortellini, A, Friedlaender, A, Banna, G, Porzio, G, Bersanelli, M, Cappuzzo, F, Aerts, J, Giusti, R, Bria, E, Cortinovis, D, Grossi, F, Migliorino, M, Galetta, D, Passiglia, F, Berardi, R, Mazzoni, F, Di Noia, V, Signorelli, D, Tuzi, A, Gelibter, A, Marchetti, P, Macerelli, M, Rastelli, F, Chiari, R, Rocco, D, Inno, A, Di Marino, P, Mansueto, G, Zoratto, F, Santoni, M, Tudini, M, Ghidini, M, Filetti, M, Catino, A, Pizzutilo, P, Sala, L, Occhipinti, M, Citarella, F, Marco, R, Torniai, M, Cantini, L, Follador, A, Sforza, V, Nigro, O, Ferrara, M, D'Argento, E, Leonetti, A, Pettoruti, L, Antonuzzo, L, Scodes, S, Landi, L, Guaitoli, G, Baldessari, C, Bertolini, F, Della Gravara, L, Dal Bello, M, Belderbos, R, De Filippis, M, Cecchi, C, Ricciardi, S, Donisi, C, De Toma, A, Proto, C, Addeo, A, Cantale, O, Ricciuti, B, Genova, C, Morabito, A, Santini, D, Ficorella, C, Cannita, K, Cortellini A, Friedlaender A, Banna GL, Porzio G, Bersanelli M, Cappuzzo F, Aerts JGJV, Giusti R, Bria E, Cortinovis D, Grossi F, Migliorino MR, Galetta D, Passiglia F, Berardi R, Mazzoni F, Di Noia V, Signorelli D, Tuzi A, Gelibter A, Marchetti P, Macerelli M, Rastelli F, Chiari R, Rocco D, Inno A, Di Marino P, Mansueto G, Zoratto F, Santoni M, Tudini M, Ghidini M, Filetti M, Catino A, Pizzutilo P, Sala L, Occhipinti MA, Citarella F, Marco R, Torniai M, Cantini L, Follador A, Sforza V, Nigro O, Ferrara MG, D'Argento E, Leonetti A, Pettoruti L, Antonuzzo L, Scodes S, Landi L, Guaitoli G, Baldessari C, Bertolini F, Della Gravara L, Dal Bello MG, Belderbos RA, De Filippis M, Cecchi C, Ricciardi S, Donisi C, De Toma A, Proto C, Addeo A, Cantale O, Ricciuti B, Genova C, Morabito A, Santini D, Ficorella C, and Cannita K.

Abstract

Background: The role of immune-related adverse events (irAEs), as a surrogate predictor of the efficacy of checkpoint inhibitors, has not yet been described in the setting of first-line, single-agent pembrolizumab for patients with metastatic non-small-cell lung-cancer (NSCLC) with a programmed death-ligand 1 (PD-L1) expression of ≥ 50%. Patients and methods: We previously conducted a multicenter retrospective analysis in patients with treatment-naive metastatic NSCLC and a PD-L1 expression of ≥ 50% receiving first-line pembrolizumab. Here, we report the results of the irAE analysis and the potential correlation between irAEs and clinical outcomes. Results: A total of 1010 patients were included in this analysis; after a 6-week landmark selection, 877 (86.8%) patients were included in the efficacy analysis. Any grade irAEs (P < .0001), grade 3/4 irAEs (P = .0025), leading to discontinuation irAEs (P = .0144), multiple-site and single-site irAEs (P < .0001), cutaneous irAEs (P = .0001), endocrine irAEs (P = .0227), pulmonary irAEs (P = .0479), and rheumatologic irAEs (P = .0018) were significantly related to a higher objective response rate. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0005), cutaneous irAEs (P = .0042), endocrine irAEs (P < .0001), gastrointestinal irAEs (P = .0391), and rheumatologic irAEs (P = .0086) were significantly related to progression-free survival. Any grade irAEs (P < .0001), single-site irAEs (P < .0001), multiple-site irAEs (P = .0003), cutaneous irAEs (P = .0002), endocrine irAEs (P = .0001), and rheumatologic irAEs (P = .0214) were significantly related to overall survival. Conclusions: This study confirms the feasibility and the safety of first-line, single-agent pembrolizumab, in a large, real-world cohort of patients with NSCLC with PD-L1 expression ≥ 50%. The occurrence of irAEs may be a surrogate of clinical activity and improved outcomes in this setting.

Published
2020

9. 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

10. 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

12. Smoking status during first-line immunotherapy and chemotherapy in NSCLC patients: A case–control matched analysis from a large multicenter study

Author

Cortellini, A. (Alessio), De Giglio, A. (Andrea), Cannita, K. (Katia), Cortinovis, D.L. (Diego L.), Cornelissen, R. (Robin), Baldesarri, C. (Cinzia), Giusti, R. (Raffaele), D'Argento, E. (Ettore), Grossi, F. (Francesco), Santoni, M. (Matteo), Catino, A. (Annamaria), Berardi, R. (Rossana), Sforza, V. (Vincenzo), Rossi, G. (Giovanni), Antonuzzo, L. (Lorenzo), Di Noia, V. (Vincenzo), Signorelli, D. (Diego), Gelibter, A. (Alain), Occhipinti, M.A. (Mario Alberto), Follador, A. (Alessandro), Rastelli, F. (Francesca), Chiari, R. (Rita), Gravara, L.D. (Luigi Della), Inno, A. (Alessandro), De Tursi, M. (Michele), Di Marino, P. (Pietro), Mansueto, G. (Giovanni), Zoratto, F. (Federica), Filetti, M. (Marco), Montrone, M. (Michele), Citarella, F. (Fabrizio), Pensieri, M.V. (Maria Vittoria), Russano, M. (Marco), Cantini, L. (Luca), Nigro, O. (Olga), Leonetti, A. (Alessandro), Bordi, P. (Paola), Minuti, G. (Gabriele), Landi, L. (Lorenza), De Toma, A. (Alessandro), Donisi, C. (Clelia), Ricciardi, S. (Serena), Migliorino, M.R. (Maria Rita), Napoli, V.M. (Valerio Maria), Leone, G. (Gianmarco), Metro, G. (Giulio), Banna, G.L. (Giuseppe L.), Friedlaender, A. (Alex), Addeo, A. (Alfredo), Ficorella, C. (Corrado), Porzio, G. (Giampiero), Cortellini, A. (Alessio), De Giglio, A. (Andrea), Cannita, K. (Katia), Cortinovis, D.L. (Diego L.), Cornelissen, R. (Robin), Baldesarri, C. (Cinzia), Giusti, R. (Raffaele), D'Argento, E. (Ettore), Grossi, F. (Francesco), Santoni, M. (Matteo), Catino, A. (Annamaria), Berardi, R. (Rossana), Sforza, V. (Vincenzo), Rossi, G. (Giovanni), Antonuzzo, L. (Lorenzo), Di Noia, V. (Vincenzo), Signorelli, D. (Diego), Gelibter, A. (Alain), Occhipinti, M.A. (Mario Alberto), Follador, A. (Alessandro), Rastelli, F. (Francesca), Chiari, R. (Rita), Gravara, L.D. (Luigi Della), Inno, A. (Alessandro), De Tursi, M. (Michele), Di Marino, P. (Pietro), Mansueto, G. (Giovanni), Zoratto, F. (Federica), Filetti, M. (Marco), Montrone, M. (Michele), Citarella, F. (Fabrizio), Pensieri, M.V. (Maria Vittoria), Russano, M. (Marco), Cantini, L. (Luca), Nigro, O. (Olga), Leonetti, A. (Alessandro), Bordi, P. (Paola), Minuti, G. (Gabriele), Landi, L. (Lorenza), De Toma, A. (Alessandro), Donisi, C. (Clelia), Ricciardi, S. (Serena), Migliorino, M.R. (Maria Rita), Napoli, V.M. (Valerio Maria), Leone, G. (Gianmarco), Metro, G. (Giulio), Banna, G.L. (Giuseppe L.), Friedlaender, A. (Alex), Addeo, A. (Alfredo), Ficorella, C. (Corrado), and Porzio, G. (Giampiero)

Abstract

Background: Improved outcome in tobacco smoking patients with non-small cell lung cancer (NSCLC) following immunotherapy has previously been reported. However, little is known regarding this association during first-line immunotherapy in patients with high PD-L1 expression. In this study we compared clinical outcomes according to the smoking status of two large multicenter cohorts. Methods: We compared clinical outcomes according to the smoking status (never smokers vs. current/former smokers) of two retrospective multicenter cohorts of metastatic NSCLC patients, treated with first-line pembrolizumab and platinum-based chemotherapy. Results: A total of 962 NSCLC patients with PD-L1 expression ≥50% who received first-line pembrolizumab and 462 NSCLC patients who received first-line platinum-based chemotherapy were included in the study. Never smokers were confirmed to have a significantly higher risk of disease progression (hazard ratio [HR] = 1.49 [95% CI: 1.15–1.92], p = 0.0022) and death (HR = 1.38 [95% CI: 1.02–1.87], p = 0.0348) within the pembrolizumab cohort. On the contrary, a nonsignificant trend towards a reduced risk of disease progression (HR = 0.74 [95% CI: 0.52–1.05], p = 0.1003) and death (HR = 0.67 [95% CI: 0.45–1.01], p = 0.0593) were reported for never smokers within the chemotherapy cohort. After a random case–control matching, 424 patients from both cohorts were paired. Within the matched pembrolizumab cohort, never smokers had a significantly shorter progression-free survival (PFS) (HR = 1.68 [95% CI: 1.17–2.40], p = 0.0045) and a nonsignificant trend towards a shortened overall survival (OS) (HR = 1.32 [95% CI: 0.84–2.07], p = 0.2205). On the contrary, never smokers had a significantly longer PFS (HR = 0.68 [95% CI: 0.49–0.95], p = 0.0255) and OS (HR = 0.66 [95% CI: 0.45–0.97], p = 0,0356) compared to current/former smoker patients within the matched chemotherapy cohort. On pooled multivariable analysis, the interaction term between smoking stat

Published
2021
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13. Single‐institution study of correlations between skeletal muscle mass, its density, and clinical outcomes in non‐small cell lung cancer patients treated with first‐line chemotherapy

Author

Cortellini, A., Palumbo, P., Porzio, G., Verna, L., Giordano, A. V., Masciocchi, C., Parisi, A., Cannita, K., Ficorella, C., and Bozzetti, F.

Subjects
Adult, Male, Lung Neoplasms, NSCLC, muscle density, sarcopenia, BMI, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Humans, Body Weights and Measures, Non-Small-Cell Lung, Muscle, Skeletal, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Aged, 80 and over, Carcinoma, Skeletal, Original Articles, Organ Size, Middle Aged, Prognosis, lung cancer, Female, Neoplasm Grading, Treatment Outcome, Muscle, Original Article
Abstract

Background Sarcopenia and muscle tissue degradation are hallmarks of the majority of chronic diseases, including non‐small cell lung cancer (NSCLC). A computed tomography scan could be an easy modality to estimate the skeletal muscle mass through cross‐sectional image analysis at the level of the third lumbar vertebra. Methods Baseline skeletal muscle mass (SMM) was evaluated through the skeletal muscle index (SMI), together with skeletal muscle radiodensity (SMD), in NSCLC patients undergoing first‐line chemotherapy to evaluate correlations with safety and clinical outcomes. When SMIs at different time points were available, further comparison was made between patients with worse and improved SMIs. Results Among 81 stage IV NSCLC patients, 28 had low SMM and 23 had low SMD. There were no significant differences in univariate analysis of progression‐free survival (PFS) between patients with baseline low and non‐low SMM (P = 0.06388) or between patients with low and non‐low SMD (P = 0.9126). Baseline low SMM, however, proved a significant predictor of shorter PFS in multivariate analysis (hazard ratio 0.54, 95% confidence interval 0.31–0.93; P = 0.0278), but not low SMD. There were no differences in overall survival (OS) between patients with baseline low and non‐low SMM or low and non‐low SMD. No differences in PFS and OS between evaluable patients with worse or improved SMI were found. A significant difference in hematological toxicities between patients with baseline low and non‐low SMM (P = 0.0358) was observed. Conclusions Low SMM is predictive of shorter PFS, while consecutive changes in muscular mass do not seem to be a predictor of PFS or OS. The role of muscle radiodensity remains a matter of debate.

Published
2018

14. Evaluation of second-line anti-VEGF after first-line anti-EGFR based therapy in RAS wild-type metastatic colorectal cancer. The multicenter 'SLAVE' study

Author

Parisi, A., Cortellini, A., Cannita, K., Venditti, O., Camarda, F., Calegari, M. A., Salvatore, L., Tortora, G., Rossini, D., Germani, M. M., Boccaccino, A., Dell&apos, aquila, E., Fulgenzi, C., Santini, D., De Tursi, M., Tinari, N., Di Marino, P., Lombardi, P., Keranen, S. R., Alvaro, M. H., Zurlo, I. V., Corsi, D. C., Emiliani, A., Zanaletti, N., Troiani, T., Vitale, P., Giampieri, R., Merloni, F., Occhipinti, M., Marchetti, P., Roberto, M., Mazzuca, F., Ghidini, M., Indini, A., Garajova, I., Zoratto, F., Monache, S. D., Porzio, G., and Ficorella, C.

Subjects
aflibercept, anti-angiogenics, bevacizumab, cetuximab, panitumumab, ras wild-type mcrc, second-line treatment
Published
2020

16. 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

17. 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, Alessandra, 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., Cassano A. (ORCID:0000-0002-3311-7163), 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, Alessandra, 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., Cassano A. (ORCID:0000-0002-3311-7163), 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

18. 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, Alessandra, 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), Cassano A. (ORCID:0000-0002-3311-7163), 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, Alessandra, 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), Cassano A. (ORCID:0000-0002-3311-7163), 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

22. A real-life multicenter study on body weight loss and body mass index in advanced Gastric Cancer patients treated with Ramucirumab-based second-line therapy

Author

Parisi, A., primary, Cortellini, A., additional, Roberto, M., additional, Venditti, O., additional, Santini, D., additional, Dell’Aquila, E., additional, Stellato, M., additional, Marchetti, P., additional, Occhipinti, M., additional, Zoratto, F., additional, Mazzuca, F., additional, Tinari, N., additional, De Tursi, M., additional, Iezzi, L., additional, Natoli, C., additional, Ratti, M., additional, Pizzo, C., additional, Ghidini, M., additional, Ficorella, C., additional, and Cannita, K., additional

Published
2019
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26. Clinical and psychometric validation of the BreSAS questionnaire for symptom assessment among breast cancer survivors

Author

Giusti, R., primary, Scarpi, E., additional, Cannita, K., additional, Silva, R.R., additional, Filetti, M., additional, Mazzotta, M., additional, Rossi, R., additional, Cocciolone, V., additional, Sidoni, T., additional, Tudini, M., additional, Ficorella, C., additional, Botticelli, A., additional, Marchetti, P., additional, Porzio, G., additional, and Verna, L., additional

Published
2018
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27. Timed-flat infusion (TFI) 5-fluorouracil with irinotecan and oxaliplatin in pancreatic adenocarcinomas: A single institution experience with FIr/FOx regimen

Author

Cortellini, A., primary, Parisi, A., additional, Cannita, K., additional, Venditti, O., additional, Pavese, F., additional, D'Orazio, C., additional, Lanfiuti Baldi, P., additional, Vicentini, V., additional, Vicentini, R., additional, Porzio, G., additional, Verna, L., additional, and Ficorella, C., additional

Published
2018
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28. Abstract P1-17-02: Ado-trastuzumab emtansine (TDM-1) treatment and brain metastases in HER2 positive metastatic breast cancer patients: Final analysis of an italian multicenter study

Author

Fabi, A, primary, Alesini, D, additional, Valle, E, additional, Carbognin, L, additional, Arpino, G, additional, Montemurro, F, additional, Ciccarese, M, additional, Cannita, K, additional, Paris, I, additional, Cursano, MC, additional, Moscetti, L, additional, Ferretti, G, additional, De Laurentiis, M, additional, Zambelli, A, additional, La Verde, N, additional, Nisticò, C, additional, Gasparro, S, additional, Giannarelli, D, additional, and Cognetti, F, additional

Published
2018
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29. Brain metastases and ado-trastuzumab emtansine (TDM-1) treatment in HER2 positive metastatic patients: an Italian multicenter analysis

Author

Fabi, A., primary, Alesini, D., additional, Valle, E., additional, Carbognin, L., additional, Arpino, G., additional, Santini, D., additional, Montemurro, F., additional, Ciccarese, M., additional, Cannita, K., additional, Paris, I., additional, Moscetti, L., additional, De Laurentiis, M., additional, Zambelli, A., additional, La Verde, N., additional, Nisticò, C., additional, Ferretti, G., additional, Gasparro, S., additional, Giannarelli, D., additional, and Cognetti, F., additional

Published
2017
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30. A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: a real- world experience

Author

Vici, P, Pizzuti, L, Michelotti, A, Sperduti, I, Natoli, C, Mentuccia, L, Di Lauro, L, Sergi, Daniele, Marchetti, Paolo, Santini, D, Magnolfi, E, Iezzi, L, Moscetti, L, Fabbri, Alessandro, Cassano, Alessandra, Grassadonia, A, Omarini, C, Piacentini, Francesca, Botticelli, A, Bertolini, I, Scinto, Af, Zampa, G, Mauri, Marco, D'Onofrio, L, Sini, V, Barba, Marta, Maugeri-Saccà, M, Rossi, Ernesto, Landucci, E, Tomao, S, Alberti, Andrea Maria, Giotta, F, Ficorella, C, Adamo, V, Russo, A, Lorusso, Vito, Cannita, K, Barni, S, Laudadio, L, Greco, F, Garrone, O, Della Giulia, M, Marolla, P, Sanguineti, G, Di Cocco, B, Ciliberto, G, De Maria Marchiano, Ruggero, Gamucci, Teresa, Sergi D, Marchetti P, Fabbri A, Cassano A (ORCID:0000-0002-3311-7163), Barba M (ORCID:0000-0001-6084-7666), Rossi E, Alberti AM, Lorusso V, De Maria Marchiano R (ORCID:0000-0003-2255-0583), Gamucci T., Vici, P, Pizzuti, L, Michelotti, A, Sperduti, I, Natoli, C, Mentuccia, L, Di Lauro, L, Sergi, Daniele, Marchetti, Paolo, Santini, D, Magnolfi, E, Iezzi, L, Moscetti, L, Fabbri, Alessandro, Cassano, Alessandra, Grassadonia, A, Omarini, C, Piacentini, Francesca, Botticelli, A, Bertolini, I, Scinto, Af, Zampa, G, Mauri, Marco, D'Onofrio, L, Sini, V, Barba, Marta, Maugeri-Saccà, M, Rossi, Ernesto, Landucci, E, Tomao, S, Alberti, Andrea Maria, Giotta, F, Ficorella, C, Adamo, V, Russo, A, Lorusso, Vito, Cannita, K, Barni, S, Laudadio, L, Greco, F, Garrone, O, Della Giulia, M, Marolla, P, Sanguineti, G, Di Cocco, B, Ciliberto, G, De Maria Marchiano, Ruggero, Gamucci, Teresa, Sergi D, Marchetti P, Fabbri A, Cassano A (ORCID:0000-0002-3311-7163), Barba M (ORCID:0000-0001-6084-7666), Rossi E, Alberti AM, Lorusso V, De Maria Marchiano R (ORCID:0000-0003-2255-0583), and Gamucci T.

Abstract

We addressed trastuzumab emtansine (T-DM1) e cacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab- pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing signi cant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical bene t 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no di erences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab- pretreated (p=0.13), and 6 and 22 months in pertuzumab-naïve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-naïve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab- pretreated (p=0.05) and 6 and 17 months in pertuzumab-naïve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival bene t (p<0.0001), while overall survival was positively a ected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical bene t (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to con rm and interpret our data on apparently lower T-DM1 e cacy when given as second-line treatment after pertuzumab, and on the optimal sequence order.

Published
2017

32. Abstract P4-21-11: T-DM1 in HER2 positive advanced breast cancer patients: Real world practice from a multicenter observational study

Author

Fabi, A, primary, De Laurentiis, M, additional, Caruso, M, additional, Valle, E, additional, Moscetti, L, additional, Santini, D, additional, Cannita, K, additional, Carbognin, L, additional, Ciccarese, M, additional, Rossello, R, additional, Arpino, G, additional, Leonardi, V, additional, Montemurro, F, additional, La Verde, N, additional, Generali, DG, additional, Zambelli, A, additional, Scandurra, G, additional, Russillo, M, additional, Paris, I, additional, D'Ottavio, AM, additional, Filippelli, G, additional, Giampaglia, M, additional, Stani, S, additional, Fabbri, A, additional, Alesini, D, additional, Giannarelli, D, additional, and Cognetti, F, additional

Published
2017
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33. Novel P53 mutations detected by FAMA in colorectal cancers

Author

DE GALITIIS, F, Cannita, K, Tessitore, A, Martella, F, DI ROCCO ZC, Russo, A, Adamo, V, Iacobelli, S, Martinotti, S, Marchetti, Paolo, Ficorella, C, Ricevuto, E, CONSORZIO INTERUNIVERSITARIO NAZIONALE BIO ONCOLOGIA, DE GALITIIS F, CANNITA K, TESSITORE A, MARTELLA F, DI ROCCO ZC, RUSSO A, ADAMO V, IACOBELLI S, MARTINOTTI S, MARCHETTI P, FICORELLA C, and RICEVUTO E

Subjects
Oncology, medicine.medical_specialty, Mutant, DNA Mutational Analysis, Mutation, Missense, Gene mutation, medicine.disease_cause, Exon, Internal medicine, medicine, Missense mutation, Humans, Key words: colon cancer, p53, mutations, FAMA, Allele, Gene, Mutation, business.industry, Hematology, DNA, Neoplasm, Exons, Genes, p53, Molecular biology, business, Colorectal Neoplasms, Heteroduplex
Abstract

Background The aim of the study was to identify p53 gene mutations by FAMA (fluorescence-assisted mismatch analysis) in colorectal cancers. Patients and methods Analytical scanning of the p53 gene (exons 5–9) was performed in colon cancer samples from 44 consecutive patients by FAMA. FAMA is a semiautomatic scanning approach based on the chemical cleavage of the mismatch in fluorescently labeled heteroduplex DNA, obtained from the combination of a normal and a mutated allele. FAMA has already shown optimal levels of diagnostic accuracy and sensitivity in detecting gene mutations (nucleotide substitutions, insertions/deletions) both at the germline and somatic level. The peculiar feature of FAMA is its ability to detect and localize mutations, by a redundant pattern of signals due to fluorescent DNA fragments generated by chemical cleavage. Moreover, previous data have demonstrated that normal contaminating DNA from stromal cells in the sample does not affect the sensitivity of the procedure, leading to the identification of the mutation even when the ratio mutant/normal allele is 10%. Results Eighteen mutations (12 missense, one nonsense, two deletions, three nucleotide substitutions at the level of the splice-junctions) and two polymorphisms were detected by FAMA in 17 patients (39%) and then confirmed by automated sequence analysis. Six of 18 mutations (33%) were not previously reported for colon cancer samples and two of 18 lesions (11%) were identified as novel p53 mutations. Conclusions Analytical scanning of the p53 gene by FAMA in DNA from colon cancer samples provides a sensitive, accurate and specific diagnostic procedure for routine clinical application.

Published
2006

34. Italian observational study on T-DM1 in HER2 positive advanced breast cancer patients: real world effectiveness and safety

Author

Fabi, A., primary, Alesini, D., additional, De Laurentiis, M., additional, Valle, E., additional, Santini, D., additional, Cannita, K., additional, Carbognin, L., additional, Ciccarese, M., additional, Arpino, G., additional, Leonardi, V., additional, Montemurro, F., additional, La Verde, N., additional, Generali, D.G., additional, Scandurra, G., additional, Russillo, M., additional, Paris, I., additional, D'Ottavio, A.M., additional, Filippelli, G., additional, Stani, S., additional, Giannarelli, D., additional, and Cognetti, F., additional

Published
2016
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35. Bioclinical Parameters Driving Decision-Making of Subsequent Lines of Treatment in Metastatic Castration-Resistant Prostate Cancer

Author

Irelli, A., Bruera, G., Cannita, K., Palluzzi, E., Gravina, G. L., Festuccia, C., Ficorella, C., and Ricevuto, E.

Subjects
Article Subject
Abstract

Different options are available as second-line treatment of metastatic castrate-resistant prostate cancer: cabazitaxel, abiraterone, and enzalutamide. Phase III studies evaluating cabazitaxel and the two hormonal agents have been shown to significantly prolong overall survival compared to mitoxantrone and placebo, respectively. Several studies have also demonstrated feasibility and activity of docetaxel rechallenge in case of a sufficient progression-free interval (3–6 months), good performance status, and previous acceptable safety profile, thus providing an additional treatment option in clinical practice. Clinical and biological parameters should be considered to tailor II line treatment. In clinical practice, we can primarily evaluate patients’ fitness according to age, performance status, symptomatic disease, comorbidities, and expected safety profile of each drug. Different prognostic/predictive factors may be considered, such as presence of bone-limited or visceral metastases, length of androgen deprivation therapy (ADT) before chemotherapy, time to progression after docetaxel, Gleason score, PSA doubling time, and serum testosterone, even if their clinical relevance is still debated. This review will discuss current options of innovative drugs sequencing and selection according to bioclinical parameters.

Published
2014
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44. [Oxaliplatin: preclinical in vitro studies]

Author

Marchetti P, Carlo G, Cappellini A, Porzio G, Enrico RICEVUTO, Cannita K, and Ficorella C

Subjects
Oxaliplatin, Cyclohexylamines, Leukemia, Organoplatinum Compounds, Tumor Cells, Cultured, Animals, Humans, Antineoplastic Agents, DNA, Neoplasm, Colorectal Neoplasms
Published
2002

46. Effectiveness of liver metastasectomies in patients with metastatic colorectal cancer treated with FIr-B/FOx Triplet Chemotherapy plus Bevacizumab

Author

Bruera, G, Cannita, K, Giuliante, Felice, Baldi, Pl, Vicentini, R, Marchetti, P, Nuzzo, Gennaro, Antonucci, A, Ficorella, C, Ricevuto, E., Giuliante, Felice (ORCID:0000-0001-9517-8220), Bruera, G, Cannita, K, Giuliante, Felice, Baldi, Pl, Vicentini, R, Marchetti, P, Nuzzo, Gennaro, Antonucci, A, Ficorella, C, Ricevuto, E., and Giuliante, Felice (ORCID:0000-0001-9517-8220)

Abstract

BACKGROUND: Intensive medical treatment increases resection rate of liver metastases in patients with metastatic colorectal cancer (MCRC). The effectiveness of liver metastasectomies was evaluated in patients with MCRC who were treated with previously reported FIr-B/FOx (triplet chemotherapy plus bevacizumab). PATIENTS AND METHODS: Fifty patients with MCRC enrolled in the reported phase II study were classified according to involved metastatic sites (liver-only metastatic site, multiple metastatic sites) and the extent of liver metastases (single, multiple). Surgical resectability of liver metastases was evaluated at baseline and every 3 cycles of FIr-B/FOx treatment. The resection rate of liver metastases, activity, and efficacy were evaluated; progression-free survival (PFS) and overall survival (OS) were compared by using the log-rank test. RESULTS: Patients with liver MCRC were 33 of 50 consecutive unselected patients with MCRC: liver limited, 22 patients; multiple metastatic sites, 11 patients. Liver metastasectomies were performed in 13 patients: 26% of 50 patients with MCRC, 39% of 33 patients with liver MCRC. In patients with liver-only MCRC, a secondary liver surgery was performed in 54%: 6 of 9 single and 6 of 13 multiple liver metastases. Also, 1 liver and lung metastasectomy was performed. Pathologic complete responses were achieved in 2 patients (15%). The conversion rate of unresectable liver metastases was 83%. Objective response rate, PFS, OS were, respectively: 84%, 11 and 23 months in 33 liver MCRC; 86%, 17 and 44 months in 22 liver-limited patients. PFS and OS were significantly increased in patients with liver-limited metastases compared with multiple metastatic sites and single compared with multiple liver metastases. CONCLUSION: The FIr-B/FOx regimen may increase the resection rate of liver metastases and improve clinical outcome of patients with liver-only MCRC.

Published
2012

49. p16 (INK4a, MTS-1) gene polymorphism and methylation status in human pituitary tumors

Author

Jaffrain, MARIE LISE, Ferretti, E, Toniato, E, Cannita, K, Santoro, A, DI STEFANO, D, Ricevuto, Enrico, Maroder, M, Tamburrano, G, Cantore, G, Gulino, A, and Martinotti, S.

Subjects
Adenoma, Adult, Male, pituitary tumorigenesis, Polymorphism, Genetic, Genes, p16, p16, Pituitary tumours, DNA Methylation, Middle Aged, Polymerase Chain Reaction, Pituitary tumours, p16, methylation, pituitary tumorigenesis, Growth Hormone, Multiple Endocrine Neoplasia Type 1, Humans, Female, Pituitary Neoplasms, methylation, Gene Silencing, Follicle Stimulating Hormone, Polymorphism, Single-Stranded Conformational, Aged
Abstract

The p16 gene, which encodes a physiological inhibitor of the cyclin D-CDK4 complex, is now considered as an important tumour-suppressor gene in a variety of tumours. A marked reduction of its expression has been reported to occur without significant genetic alterations in human pituitary adenomas, although rare point mutations of uncertain functional significance have been described. On the other hand, p16 gene silencing due to hypermethylation has been reported in several human primary tumours. The aim of this study was to further investigate the pathogenetic events leading to p16 gene inactivation in pituitary tumours.To screen a european series of human pituitary tumours for p16 gene alterations and possible gene hypermethylation.A representative series of 31 human pituitary tumours-30 macroadenomas, including a MEN-1 non-secreting pituitary adenoma and a non-MEN-1 familial giant GH-secreting adenoma, and one FSH-secreting pituitary carcinoma-was studied.Polymerase chain reaction/single strand conformation polymorphism (PCR-SSCP) analysis was used to screen for p16 gene alterations in all cases. Direct sequencing of PCR-products was obtained by the di-deoxynucleotide method where suspected abnormalities of the PCR-SSCP analysis were observed. In 24 samples, a methylation-specific PCR assay (MSP-PCR) was used to determine p16 gene methylation status.Two sporadic cases of pituitary adenomas had a similar single A to G base substitution leading to an heterozygous Ala140Thr p16 polymorphism, which has not previously been described in such tumours, but is known to be functionally silent. No other p16 abnormality could be suspected from PCR-SSCP analysis in this series. In contrast, the presence of methylated-specific PCR products was observed in 20/24 cases (83.3%).This study confirms that p16 gene mutations are not involved in the pathogenesis of human pituitary tumours, although polymorphisms can be demonstrated, depending on the population considered. In contrast, the high incidence of hypermethylation of the p16 gene suggests that such an alteration occurs early in pituitary tumours, and may play a role in pituitary tumorigenesis.

Published
1999

50. Molecular diagnosis of p53 mutations in gastric carcinoma by touch preparation

Author

Enrico RICEVUTO, Ficorella, C., Fusco, C., Cannita, K., Tessitore, A., Toniato, E., Gabriele, A., Frati, L., Marchetti, P., Gulino, A., and Martinotti, S.

Subjects
Base Sequence, Molecular Sequence Data, DNA, Neoplasm, Exons, Genes, p53, Polymerase Chain Reaction, Stomach Neoplasms, Mutation, Humans, Point Mutation, Polymorphism, Single-Stranded Conformational, DNA Primers, Neoplasm Staging, Research Article
Abstract

Thirty-one tumor samples from selected cases of gastric carcinoma were analyzed for mutations of the p53 tumor suppressor gene. Template DNA was prepared according to the touch preparation procedure, which allowed us to isolate clusters of neoplastic cells out of a stromal cellular background to be used as a template in the amplification of target exons of the p53 locus. In our present study, by polymerase chain reaction/single strand conformation polymorphism analysis we give evidence of p53 mutations occurring in the DNA-binding core domain of the protein (exons 5 through 9), which are clustered in stages III and IV of the disease (six mutations out of seventeen samples; 35%). No p53 mutations were detected in fourteen gastric cancer samples at I and II stages. Beside the use of conventional molecular scanning procedures, our study proposes the application of the touch preparation method to increase the detection of genetic alterations in human solid tumors.

Published
1996

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