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26 results on '"Natoli, C."'

1. Breast cancer 'tailored follow-up' in Italian oncology units: a web-based survey

Author

Natoli, C., Brocco, D., Sperduti, I., Nuzzo, A., Tinari, N., De Tursi, M., Grassadonia, A., Mazzilli, L., Iacobelli, S., Gamucci, T., Vici, P., Study, Group, Adamo, V., Airoldi, M., Amoroso, D., Angelini, F., Angiolini, C., Angiolucci, G., Ardizzoia, A., Baldini, E., Ballardini, P., Barni, S., Barone, C., Battelli, N., Bernardi, D., Bianchetti, S., Bianco, N., Biglia, Nicoletta, Bilancia, D., Biti, G., Boni, C., Bordonaro, R., Botta, M., Bretti, S., Brunello, A., Brunetti, C., Bruno, D., Bucci, E., Buzzoni, R., Cagossi, K., Cappelletti, C., Cappuzzo, F., Cardillo, F., Carroccio, R., Cascinu, S., Cavanna, L., Cianchetti, E., Clerico, M., Contu, A., Corsi, D., Cortesi, L., Cretella, E., Crispino, S., Di Lieto, M., Di Lullo, L., Durini, E., Fabi, A., Failla, G., Fattorusso, S., Ferraù, F., Ferro, A., Ficorella, C., Fogazzi, G., Foglietta, J., Francini, G., Fusco, O., Gennari, A., Ghiani, M., Gianni, L., Giordano, M., Giotta, F., Giuliani, R., Gori, S., Graiff, C., Guarneri, V., Guarneri, D., Guglielmi, F., Landriscina, M., Laudadio, L., Lombardo, M., Longo, F., Macellari, G., Madeddu, C., Magnanini, S., Maiorino, L., Mangiameli, A., Marini, G., Massidda, B., Mattioli, R., Michelotti, A., Molino, A., Montesarchio, V., Morale, A., Murgo, R., Naso, G., Natale, D., Orditura, M., Orrù, S., Pace, R., Palazzo, A., Palma, F., Pancotti, A., Pandoli, G., Papaldo, P., Parisi, A. M., Passalacqua, R., Pellegrino, A., Perrucci, B., Proietti, E., Recchia, F., Riccardi, F., Rispoli, A. I., Rocca, A., Romaniello, I., Rossetti, R., Rossi, D., Rosti, G., Ruggeri, E. M., Russo, A., Savarino, A., Savastano, C., Scognamiglio, G., Scognamiglio, M., Seminara, P., Serrachini, S., Sidoti, V., Silva, R. R., Surace, G., Tomao, S., Tonini, G., Trenta, P., Turazza, M., Valenza, R., Veltri, E., Zampa, G., Zaniboni, A., Zanirato, S., C, Natoli, D, Brocco, I, Sperduti, A, Nuzzo, N, Tinari, M, De Tursi, A, Grassadonia, L, Mazzilli, S, Iacobelli, T, Gamucci, P, Vici, Study Group, 'FOLLOW-UP', and Orditura, Michele

Subjects
Oncology, breast cancer, Follow-up, survey, Medical Oncology, law.invention, Randomized controlled trial, law, Aged, Breast Neoplasms, Female, Follow-Up Studies, Health Care Surveys, Humans, Italy, Middle Aged, Secondary Prevention, Guideline Adherence, Breast Tumors, Medicine and Health Sciences, Web based survey, Multidisciplinary, Pharmaceutics, Surgical Oncology, Cancer Therapy, Medicine, medicine.symptom, Disease staging, Research Article, medicine.medical_specialty, Adjuvant Cancer Chemotherapy, Science, MEDLINE, Asymptomatic, Breast cancer, Drug Therapy, Internal medicine, medicine, Cancer Detection and Diagnosis, Chemotherapy, Modalities, business.industry, Cancers and Neoplasms, medicine.disease, Blood chemistry, Women's Health, Clinical Medicine, business
Abstract

PurposeBreast cancer follow-up procedures after primary treatment are still a controversial issue. Aim of this study was to investigate, through a web-based survey, surveillance methodologies selected by Italian oncologists in everyday clinical practice.MethodsReferents of Italian medical oncology units were invited to participate to the study via e-mail through the SurveyMonkey website. Participants were asked how, in their institution, exams of disease staging and follow-up are planned in asymptomatic women and if surveillance continues beyond the 5th year.ResultsBetween February and May 2013, 125 out of 233 (53.6%) invited referents of Italian medical oncology units agreed to participate in the survey. Ninety-seven (77.6%) referents state that modalities of breast cancer follow-up are planned according to the risk of disease progression at diagnosis and only 12 (9.6%) oncology units apply the minimal follow-up procedures according to international guidelines. Minimal follow-up is never applied in high risk asymptomatic women. Ninety-eight (78.4%) oncology units continue follow-up in all patients beyond 5 years.ConclusionsOur survey shows that 90.4% of participating Italian oncology units declare they do not apply the minimal breast cancer follow-up procedures after primary treatment in asymptomatic women, as suggested by national and international guidelines. Interestingly, about 80.0% of interviewed referents performs the so called "tailored follow-up", high intensity for high risk, low intensity for low risk patients. There is an urgent need of randomized clinical trials able to determine the effectiveness of risk-based follow-up modalities, their ideal frequency and persistence in time.

Published
2014

2. High expression of 90K (Mac-2 BP) is associated with poor survival in node-negative breast cancer patients not receiving adjuvant systemic therapies

Author

Tinari, N., Lattanzio, R., Querzoli, P., Natoli, C., Grassadonia, A., Alberti, S., Hubalek, M., Reimer, D., Nenci, I., Bruzzi, P., Piantelli, M., Iacobelli, S., and Consorzio Interuniversitario Nazionale per la Bio-Oncologia

Subjects
Oncology, Risk, medicine.medical_specialty, Pathology, Cancer Research, Multivariate analysis, medicine.medical_treatment, Breast Neoplasms, Disease, 90K, Breast cancer, Prognosis, Lower risk, Models, Biological, Disease-Free Survival, NO, 90K, breast cancer, prognosis, Adjuvants, Immunologic, Antigens, Neoplasm, Internal medicine, medicine, Humans, Aged, Membrane Glycoproteins, business.industry, Hazard ratio, Middle Aged, medicine.disease, Immunohistochemistry, Node negative, Gene Expression Regulation, Neoplastic, Treatment Outcome, Multivariate Analysis, Female, business, Adjuvant
Abstract

90K (Mac-2 BP) expression was evaluated by immunohistochemistry in paraffin-embedded tissue from a consecutive series of lymph-node negative breast cancer patients who did not receive adjuvant systemic treatment. An independent series of patients served as validation set. The association of 90K expression with risk of recurrence and death was examined in survival analyses together with known prognostic factors. High levels of 90K expression (IHC score > 8) were observed in 43 (25.3%) of 170 tumors examined. We found elevated risks of distant recurrence and overall mortality in patients with high 90K expression compared with patients with low 90K expression in their tumors. This increase persisted after adjusting for other prognostic factors in multivariate analysis (hazard ratio = 4.084; p < 0.001 for recurrence; hazard ratio = 4.298; p < 0.001 for death). These findings were confirmed in the validation set. Therefore, evaluation of 90K expression may be beneficial to identify lymph-node negative breast cancer patients at lower risk of disease recurrence and death. © 2008 Wiley-Liss, Inc.

Published
2008

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

Author

Pietro Del Medico, Rossana Berardi, Enzo Veltri, Maria Rosaria Valerio, Alessandra Cassano, Daniele Marinelli, Vito Lorusso, Patrizia Vici, Nicola D’Ostilio, Silverio Tomao, Enrico Cortesi, Nicola Tinari, Emilio Bria, Domenico Sergi, Luca Moscetti, Giuseppe Sanguineti, Teresa Gamucci, Claudio Zamagni, Maddalena Barba, Clara Natoli, Theodora Daralioti, Giancarlo Paoletti, Antonino Grassadonia, Marina Elena Cazzaniga, Icro Meattini, Ornella Garrone, Andrea Michelotti, Giuseppina Sarobba, Nicla La Verde, Laura Pizzuti, Letizia Perracchio, Vincenzo Adamo, Giuseppe Tonini, A. Vaccaro, Francesco Giotta, Corrado Ficorella, Maria Agnese Fabbri, Antonio Russo, Paolo Marchetti, Gennaro Ciliberto, Mirco Pistelli, Rosanna Mirabelli, Marco Mazzotta, Daniele Generali, Marcello Maugeri-Saccà, Mario Roselli, Angelo Di Leo, Anna Di Benedetto, Isabella Sperduti, Ida Paris, Eriseld Krasniqi, Carlo Garufi, Lorenzo Livi, Ruggero De Maria, Andrea Botticelli, Domenico Corsi, 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, Laura, Barba, Maddalena, Mazzotta, Marco, Krasniqi, Eriseld, Maugeri-Saccà, Marcello, Gamucci, Teresa, Berardi, Rossana, Livi, Lorenzo, Ficorella, Corrado, Natoli, Clara, Cortesi, Enrico, Generali, Daniele, La Verde, Nicla, Cassano, Alessandra, Bria, Emilio, Moscetti, Luca, Michelotti, Andrea, Adamo, Vincenzo, Zamagni, Claudio, Tonini, Giuseppe, Sergi, Domenico, Marinelli, Daniele, Paoletti, Giancarlo, Tomao, Silverio, Botticelli, Andrea, Marchetti, Paolo, Tinari, Nicola, Grassadonia, Antonino, Valerio, Maria Rosaria, Mirabelli, Rosanna, Fabbri, Maria Agnese, D’Ostilio, Nicola, Veltri, Enzo, Corsi, Domenico, Garrone, Ornella, Paris, Ida, Sarobba, Giuseppina, Meattini, Icro, Pistelli, Mirco, Giotta, Francesco, Lorusso, Vito, Garufi, Carlo, Russo, Antonio, Cazzaniga, Marina, Del Medico, Pietro, Roselli, Mario, Vaccaro, Angela, Perracchio, Letizia, di Benedetto, Anna, Daralioti, Theodora, Sperduti, Isabella, De Maria, Ruggero, Di Leo, Angelo, Sanguineti, Giuseppe, Ciliberto, Gennaro, Vici, Patrizia, 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.

Subjects
0301 basic medicine, Oncology, Cancer therapy, Receptor, ErbB-2, medicine.medical_treatment, Ado-Trastuzumab Emtansine, progesterone receptor, Settore MED/06, 0302 clinical medicine, human epidermal growth factor receptor 2 (HER2), Antineoplastic Combined Chemotherapy Protocols, estrogen, Neoplasm Metastasis, skin and connective tissue diseases, Multidisciplinary, Brain Neoplasms, Middle Aged, Prognosis, Metastatic breast cancer, Neoplasm Metastasi, 030220 oncology & carcinogenesis, Medicine, Female, Pertuzumab, metastatic breast cancer, Receptors, Progesterone, Breast Neoplasm, HER2 positivity, medicine.drug, Human, Adult, medicine.medical_specialty, medicine.drug_class, Science, trastuzumab-emtansine, Breast Neoplasms, cancer, Article, Disease-Free Survival, Brain Neoplasm, 03 medical and health sciences, Breast cancer, breast cancer, Settore MED/04 - PATOLOGIA GENERALE, pertuzumab, Internal medicine, Progesterone receptor, medicine, Humans, neoplasms, Aged, Chemotherapy, Antineoplastic Combined Chemotherapy Protocol, business.industry, Cancer, medicine.disease, HER2-positive, oncology, radiotherapy, chemotherapy, HER2, Radiation therapy, 030104 developmental biology, Estrogen, business, prognostic relevance
Abstract

Breast cancer (BC) heterogeneity is composite in nature, with a wide variety of factors concurring to define several pathological entities, which differ by clinical presentation, pathologic features, therapy administered, and inherent outcomes1. Additional sources of breast cancer heterogeneity may raise during the disease course. In BC patients whose disease was initially diagnosed in the early stage and subsequently progressed with metastatic involvement of one single or multiple site/s, the molecular characteristics of metastatic lesions do not necessary mimic those of the disease initially diagnosed. A well-depicted molecular landscape is crucial for subtype definition, prognostic evaluation and appropriate therapeutic decisions. Accordingly, current guidelines suggest repeating the immunohistochemical (IHC) assessment in patients with metastatic spread and at least one secondary lesion amenable to biopsy2. Discordance in human epidermal growth factor receptor 2 (HER2) status between the tumor and metastatic lesions is widely acknowledged, and not yet completely unraveled in their biologic meaning and prognostic relevance3–11. The overexpression of HER2 or amplification of the related gene is extensively recognized as a feature associated with more aggressive biological behavior12,13. However, the extent to which changes in HER2 status may affect patients’ prognosis is still a matter of debate14. We herein propose an observational study of HER2-positive metastatic breast cancer (mBC) patients treated with the anti-HER2 targeted agents pertuzumab and/or trastuzumab emtansine (T-DM1). Our research question is whether relevant differences exist in long-term outcomes of patients with concordant HER2 status between the primary tumor and its secondary lesion/s compared to patients whose disease revealed HER2-positivity gain at the IHC assessment of metastatic lesions. In our historical cohorts, we also sought to identify factors associated with HER2-positivity gain at the IHC reassessment, for which an impact on prognosis may be foreseen.

Published
2021

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

Author

Nicla La Verde, Domenico Corsi, Patrizia Vici, Angelo Di Leo, Enzo Veltri, Lorenzo Livi, Marina Elena Cazzaniga, Laura Pizzuti, Pietro Del Medico, Caterina Marchiò, Maria Rosaria Valerio, Ornella Garrone, Giuseppina Sarobba, Rossella Loria, Gennaro Ciliberto, Eriseld Krasniqi, Marcello Maugeri-Saccà, Anna Sapino, Paolo Marchetti, Rossana Berardi, Rita Falcioni, Silverio Tomao, Clara Natoli, Vincenzo Adamo, Valentina Laquintana, Maddalena Barba, Claudio Zamagni, Maria Agnese Fabbri, Carlo Garufi, Giulia Bon, Giuseppe Sanguineti, Giacomo Barchiesi, Enrico Cortesi, Rosanna Mirabelli, Francesco Giotta, Nicola D’Ostilio, Giuseppe Tonini, Emilio Bria, Daniele Marinelli, Manuela Porru, Luca Moscetti, Marco Mazzotta, Ida Paris, Andrea Michelotti, Mario Roselli, Alessandra Cassano, Teresa Gamucci, Antonio Russo, Isabella Sperduti, Corrado Ficorella, Daniele Generali, Ruggero De Maria, Carlo Leonetti, 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, Giulia, Pizzuti, Laura, Laquintana, Valentina, Loria, Rossella, Porru, Manuela, Marchiò, Caterina, Krasniqi, Eriseld, Barba, Maddalena, Maugeri-Saccà, Marcello, Gamucci, Teresa, Berardi, Rossana, Livi, Lorenzo, Ficorella, Corrado, Natoli, Clara, Cortesi, Enrico, Generali, Daniele, La Verde, Nicla, Cassano, Alessandra, Bria, Emilio, Moscetti, Luca, Michelotti, Andrea, Adamo, Vincenzo, Zamagni, Claudio, Tonini, Giuseppe, Barchiesi, Giacomo, Mazzotta, Marco, Marinelli, Daniele, Tomao, Silverio, Marchetti, Paolo, Valerio, Maria Rosaria, Mirabelli, Rosanna, Russo, Antonio, Fabbri, Maria Agnese, D’Ostilio, Nicola, Veltri, Enzo, Corsi, Domenico, Garrone, Ornella, Paris, Ida, Sarobba, Giuseppina, Giotta, Francesco, Garufi, Carlo, Cazzaniga, Marina, Del Medico, Pietro, Roselli, Mario, Sanguineti, Giuseppe, Sperduti, Isabella, Sapino, Anna, De Maria, Ruggero, Leonetti, Carlo, Di Leo, Angelo, Ciliberto, Gennaro, Falcioni, Rita, Vici, Patrizia, 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, and Vici, P

Subjects
0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, Apoptosis, Ado-Trastuzumab Emtansine, Settore MED/06, chemistry.chemical_compound, 0302 clinical medicine, Trastuzumab, Antineoplastic Combined Chemotherapy Protocols, Tumor Cells, Cultured, skin and connective tissue diseases, Aged, 80 and over, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Prognosis, Gene Expression Regulation, Neoplastic, Survival Rate, 030220 oncology & carcinogenesis, Female, Pertuzumab, medicine.drug, T-DM1 efficacy, musculoskeletal diseases, Adult, medicine.medical_specialty, HER2+ breast cancer, Trastuzumab/pertuzumab blockade, Breast Neoplasms, Antibodies, Monoclonal, Humanized, lcsh:RC254-282, 03 medical and health sciences, Settore MED/04 - PATOLOGIA GENERALE, Internal medicine, medicine, Biomarkers, Tumor, Humans, neoplasms, Aged, Cell Proliferation, Retrospective Studies, Taxane, business.industry, Research, Cancer, medicine.disease, Blockade, Log-rank test, 030104 developmental biology, chemistry, Trastuzumab emtansine, Cancer cell, business
Abstract

BackgroundHER2-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.MethodsThe 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.ResultsWe 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 first-line, and 74 and 10 months in 194 pertuzumab-naïve patients (p = 0.0006 and 0.03 for OS and PFS2, respectively).ConclusionsOur data support the hypothesis that the addition of pertuzumab to trastuzumab reduces the amount of available plasma membrane HER2 receptor, limiting the binding of T-DM1 in cancer cells. This may help interpret the less favorable outcomes of second-line T-DM1 in trastuzumab/pertuzumab pre-treated patients compared to their pertuzumab-naïve counterpart.

Published
2020

5. 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

Michela Maur, A. Frassoldati, Alberto Zambelli, Antonio Febbraro, L. Livi, Raffaella Palumbo, Luca Clivio, Alessandra Fabi, D Sartori, Salvatore Artale, Ornella Garrone, A. Ferzi, N. La Verde, Marina Elena Cazzaniga, M. De Laurentiis, Lucia Mentuccia, Mariangela Ciccarese, M. Donadio, Piero Marchetti, Clara Natoli, A. Turletti, Mirco Pistelli, Claudio Scavelli, Luca Gianni, E. Romagnoli, Giancarlo Bisagni, G. Mustacchi, A. Schirone, Patrizia Vici, M. Porpiglia, M. Giordano, Daniele Generali, Livio Blasi, Andrea Michelotti, Valter Torri, Filippo Montemurro, Claudio Verusio, Giulia Bianchi, Paolo Pronzato, Corrado Ficorella, Laura Biganzoli, Ferdinando Riccardi, Francesco Atzori, L. Del Mastro, Daniele Santini, G. Moretti, A. Fumagalli, Vittorio Gebbia, Antonino Musolino, Maria Rosaria Valerio, Marta Airoldi, 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.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, and Mustacchi, G

Subjects
Oncology, medicine.medical_specialty, medicine.drug_class, Population, Anastrozole, NO, Internal medicine, Fulvestrant · First-line setting · Hormone receptor positive, Advanced breast cancer, medicine, Adjuvant therapy, Progression-free survival, education, Fulvestrant, First-Line setting, education.field_of_study, Hormone receptor positive, Aromatase inhibitor, EVA, business.industry, trials, Cancer, Endocrine Therapy, GIM-13, medicine.disease, Endocrine Therapy, HR+/HER2–, Advanced Breast Cancer, High-Dose, Fulvestrant, First-Line setting, EVA, GIM-13, AMBRA, trials, Advanced breast cancer, First-line setting, HR+/HER2–, Advanced Breast Cancer, Surgery, AMBRA, business, High-Dose, Tamoxifen, Research Article, medicine.drug
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
2019

6. 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

Sabino De Placido, Ciro Gallo, Michelino De Laurentiis, Giancarlo Bisagni, Grazia Arpino, Maria Giuseppa Sarobba, Ferdinando Riccardi, Antonio Russo, Lucia Del Mastro, Alessio Aligi Cogoni, Francesco Cognetti, Stefania Gori, Jennifer Foglietta, Antonio Frassoldati, Domenico Amoroso, Lucio Laudadio, Luca Moscetti, Filippo Montemurro, Claudio Verusio, Antonio Bernardo, Vito Lorusso, Adriano Gravina, Gabriella Moretti, Rossella Lauria, Antonella Lai, Carmela Mocerino, Sergio Rizzo, Francesco Nuzzo, Paolo Carlini, Francesco Perrone, Antonello Accurso, Biagio Agostara, Michele Aieta, Oscar Alabiso, Maria Grazia Alicicco, Dino Amadori, Laura Amaducci, Gianna Amiconi, Giustino Antuzzi, Mara Ardine, Antonio Ardizzoia, Caterina Aversa, Giuseppe Badalamenti, Sandro Barni, Carlo Basurto, Rossana Berardi, Cinzia Bergamasco, Paolo Bidoli, Claudia Bighin, Edoardo Biondi, Corrado Boni, Karen Borgonovo, Mario Botta, Stefano Bravi, Paolo Bruzzi, Giuseppe Buono, Alfredo Butera, Alessia Caldara, Giampiero Candeloro, Claudia Cappelletti, Cinzia Cardalesi, Elisabetta Carfora, Anna Cariello, Francesco Carrozza, Giacomo Cartenì, Michele Caruso, Virginia Casadei, Claudia Casanova, Luigi Castori, Luigi Cavanna, Giovanna Cavazzini, Marina Cazzaniga, Mario Chilelli, Paolo Chiodini, Silvia Chiorrini, Fortunato Ciardiello, Mariangela Ciccarese, Saverio Cinieri, Mario Clerico, Mariarosa Coccaro, Mario Comande, Claudia Corbo, Giuseppina Cortino, Stefania Cusenza, Gennaro Daniele, Alfonso Maria D'arco, Giuliana D'auria, Claudio Dazzi, Carmine De Angelis, Filippo de Braud, Gianfranco De Feo, Andrea De Matteis, Michele De Tursi, Anna Di Blasio, Giuseppe di Lucca, Liberato Di Lullo, Francesca Di Rella, Gianfranco Di Renzo, Pia Di Stefano, Aida Di Stefano, Anna Diana, Sara Donati, Agnese Fabbri, Alessandra Fabi, Marina Faedi, Gabriella Farina, Antonio Farris, Antonio Febbraro, Palma Fedele, Piera Federico, Francesco Ferraù, Gianluigi Ferretti, Antonella Ferro, Irene Floriani, Rosachiara Forcignanò, Samantha Forciniti, Valeria Forestieri, Gianni Fornari, Michela Frisinghelli, Vittorio Fusco, Giulia Gallizzi, Antonio Galvano, Antonio Gambardella, Angelo Gambi, Vittorio Gebbia, Erika Gervasi, Mara Ghilardi, Alice Giacobino, Giovanni Giardina, Francesco Giotta, Sara Giraudi, Mario Giuliano, Antonino Grassadonia, Donatella Grasso, Federica Grosso, Lorenzo Guizzaro, Pasquale Incoronato, Lorena Incorvaia, Giovanni Iodice, Nicla La Verde, Vincenzo Labonia, Gabriella Landi, Agnese Latorre, Vita Leonardi, Alessia Levaggi, Gennaro Limite, Linda Lina Bascialla, Lorenzo Livi, Evaristo Maiello, Daniela Mandelli, Ilaria Marcon, Daniela Menon, Michele Montedoro, Lucia Moraca, Anna Moretti, Maria Grazia Morritti, Patrizia Morselli, Antonella Mura, Silvia Mura, Michela Musacchio, Alberto Muzio, Donato Natale, Clara Natoli, Cinzia Nigro, Cecilia Nisticò, Antonio Nuzzo, Michele Orditura, Laura Orlando, Carmen Pacilio, Giuliano Palumbo, Raffaella Palumbo, Felice Pasini, Emanuela Paterno, Antonio Pazzola, Silvia Pelliccioni, Matilde Pensabene, Davide Perroni, Angela Pesenti Gritti, Fausto Petrelli, Maria Carmela Piccirillo, Graziella Pinotti, Claudia Pogliani, Davide Poli, Sonia Prader, Francesco Recchia, Daniele Rizzi, Carmen Romano, Rosalba Rossello, Chiara Rossini, Giuseppina Salvucci, Valeria Sanna, Alessandra Santini, Silvana Saracchini, Clementina Savastano, Giovanni Scambia, Francesco Schettini, Paola Schiavone, Alessio Schirone, Elena Seles, Simona Signoriello, Giuseppe Signoriello, Rosa Rita Silva, Antonia Silvestri, Vittorio Simeon, Ilaria Spagnoletti, Stefano Tamberi, Cristina Teragni, Verena Thalmann, Renato Thomas, Guglielmo Thomas, Amelia Tienghi, Nicola Tinari, Vincenza Tinessa, Federica Tomei, Giuseppe Tonini, Valter Torri, Divina Traficante, Marianna Tudini, Monica Turazza, Roberto Vignoli, Maria Giuseppa Vitale, Alessandra Zacchia, Pasquale Zagarese, Alda Zanni, Laura Zavallone, Maria Zavettieri, Alessandra Zoboli, 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, Ma., 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, Sabino, Gallo, Ciro, De Laurentiis, Michelino, Bisagni, Giancarlo, Arpino, Grazia, Sarobba, Maria Giuseppa, Riccardi, Ferdinando, Russo, Antonio, Del Mastro, Lucia, Cogoni, Alessio Aligi, Cognetti, Francesco, Gori, Stefania, Foglietta, Jennifer, Frassoldati, Antonio, Amoroso, Domenico, Laudadio, Lucio, Moscetti, Luca, Montemurro, Filippo, Verusio, Claudio, Bernardo, Antonio, Lorusso, Vito, Gravina, Adriano, Moretti, Gabriella, Lauria, Rossella, Lai, Antonella, Mocerino, Carmen, Rizzo, Sergio, Nuzzo, Francesco, Carlini, Paolo, Perrone, Francesco, Accurso, Antonello, Agostara, Biagio, Aieta, Michele, Alabiso, Oscar, Alicicco, Maria Grazia, Amadori, Dino, Amaducci, Laura, Amiconi, Gianna, Antuzzi, Giustino, Ardine, Mara, Ardizzoia, Antonio, Aversa, Caterina, Badalamenti, Giuseppe, Barni, Sandro, Basurto, Carlo, Berardi, Rossana, Bergamasco, Cinzia, Bidoli, Paolo, Bighin, Claudia, Biondi, Edoardo, Boni, Corrado, Borgonovo, Karen, Botta, Mario, Bravi, Stefano, Bruzzi, Paolo, Buono, Giuseppe, Butera, Alfredo, Caldara, Alessia, Candeloro, Giampiero, Cappelletti, Claudia, Cardalesi, Cinzia, Carfora, Elisabetta, Cariello, Anna, Carrozza, Francesco, Cartenì, Giacomo, Caruso, Michele, Casadei, Virginia, Casanova, Claudia, Castori, Luigi, Cavanna, Luigi, Cavazzini, Giovanna, Cazzaniga, Marina, Chilelli, Mario, Chiodini, Paolo, Chiorrini, Silvia, Ciardiello, Fortunato, Ciccarese, Mariangela, Cinieri, Saverio, Clerico, Mario, Coccaro, Mariarosa, Comande, Mario, Corbo, Claudia, Cortino, Giuseppina, Cusenza, Stefania, Daniele, Gennaro, D'arco, Alfonso Maria, D'auria, Giuliana, Dazzi, Claudio, De Angelis, Carmine, de Braud, Filippo, De Feo, Gianfranco, De Matteis, Andrea, De Tursi, Michele, Di Blasio, Anna, di Lucca, Giuseppe, Di Lullo, Liberato, Di Rella, Francesca, Di Renzo, Gianfranco, Di Stefano, Pia, Di Stefano, Aida, Diana, Anna, Donati, Sara, Fabbri, Agnese, Fabi, Alessandra, Faedi, Marina, Farina, Gabriella, Farris, Antonio, Febbraro, Antonio, Fedele, Palma, Federico, Piera, Ferraù, Francesco, Ferretti, Gianluigi, Ferro, Antonella, Floriani, Irene, Forcignanò, Rosachiara, Forciniti, Samantha, Forestieri, Valeria, Fornari, Gianni, Frisinghelli, Michela, Fusco, Vittorio, Gallizzi, Giulia, Galvano, Antonio, Gambardella, Antonio, Gambi, Angelo, Gebbia, Vittorio, Gervasi, Erika, Ghilardi, Mara, Giacobino, Alice, Giardina, Giovanni, Giotta, Francesco, Giraudi, Sara, Giuliano, Mario, Grassadonia, Antonino, Grasso, Donatella, Grosso, Federica, Guizzaro, Lorenzo, Incoronato, Pasquale, Incorvaia, Lorena, Iodice, Giovanni, La Verde, Nicla, Labonia, Vincenzo, Landi, Gabriella, Latorre, Agnese, Leonardi, Vita, Levaggi, Alessia, Limite, Gennaro, Lina Bascialla, Linda, Livi, Lorenzo, Maiello, Evaristo, Mandelli, Daniela, Marcon, Ilaria, Menon, Daniela, Montedoro, Michele, Moraca, Lucia, Moretti, Anna, Morritti, Maria Grazia, Morselli, Patrizia, Mura, Antonella, Mura, Silvia, Musacchio, Michela, Muzio, Alberto, Natale, Donato, Natoli, Clara, Nigro, Cinzia, Nisticò, Cecilia, Nuzzo, Antonio, Orditura, Michele, Orlando, Laura, Pacilio, Carmen, Palumbo, Giuliano, Palumbo, Raffaella, Pasini, Felice, Paterno, Emanuela, Pazzola, Antonio, Pelliccioni, Silvia, Pensabene, Matilde, Perroni, Davide, Pesenti Gritti, Angela, Petrelli, Fausto, Piccirillo, Maria Carmela, Pinotti, Graziella, Pogliani, Claudia, Poli, Davide, Prader, Sonia, Recchia, Francesco, Rizzi, Daniele, Romano, Carmen, Rossello, Rosalba, Rossini, Chiara, Salvucci, Giuseppina, Sanna, Valeria, Santini, Alessandra, Saracchini, Silvana, Savastano, Clementina, Scambia, Giovanni, Schettini, Francesco, Schiavone, Paola, Schirone, Alessio, Seles, Elena, Signoriello, Simona, Signoriello, Giuseppe, Silva, Rosa Rita, Silvestri, Antonia, Simeon, Vittorio, Spagnoletti, Ilaria, Tamberi, Stefano, Teragni, Cristina, Thalmann, Verena, Thomas, Renato, Thomas, Guglielmo, Tienghi, Amelia, Tinari, Nicola, Tinessa, Vincenza, Tomei, Federica, Tonini, Giuseppe, Torri, Valter, Traficante, Divina, Tudini, Marianna, Turazza, Monica, Vignoli, Roberto, Vitale, Maria Giuseppa, Zacchia, Alessandra, Zagarese, Pasquale, Zanni, Alda, Zavallone, Laura, Zavettieri, Maria, Zoboli, Alessandra, Mocerino, Carmela, D'Arco, Alfonso Maria, D'Auria, Giuliana, 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, and Zoboli, A

Subjects
Oncology, Receptor, ErbB-2, Settore MED/06 - Oncologia Medica, letrozole, law.invention, Adjuvant anastrozole, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Exemestane, law, exemestane, tamoxifen, breast cancer, Antineoplastic Combined Chemotherapy Protocols, 030212 general & internal medicine, Aromatase Inhibitors, Letrozole, Hazard ratio, Middle Aged, Receptors, Estrogen, Tolerability, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Receptors, Progesterone, Breast Neoplasm, Human, medicine.drug, medicine.medical_specialty, Socio-culturale, Anastrozole, Breast Neoplasms, Disease-Free Survival, Drug Administration Schedule, 03 medical and health sciences, Breast cancer, Internal medicine, medicine, Aromatase Inhibitor, Humans, Aged, Antineoplastic Combined Chemotherapy Protocol, Androstadiene, business.industry, medicine.disease, Androstadienes, chemistry, business, Tamoxifen
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 registered with the European Clinical Trials Database, number 2006-004018-42, and ClinicalTrials.gov, number NCT00541086. Findings: Between March 9, 2007, and July 31, 2012, 3697 patients were enrolled into the study. After a median follow-up of 60 months (IQR 46–72), 401 disease-free survival events were reported, including 211 (11%) of 1850 patients allocated to the switch strategy and 190 (10%) of 1847 patients allocated to upfront treatment. 5-year disease-free survival was 88·5% (95% CI 86·7–90·0) with the switch strategy and 89·8% (88·2–91·2) with upfront treatment (hazard ratio 0·89, 95% CI 0·73–1·08; p=0·23). 5-year disease-free survival was 90·0% (95% CI 87·9–91·7) with anastrozole (124 events), 88·0% (85·8–89·9) with exemestane (148 events), and 89·4% (87·3 to 91·1) with letrozole (129 events; p=0·24). No unexpected serious adverse reactions or treatment-related deaths occurred. Musculoskeletal side-effects were the most frequent grade 3–4 events, reported in 130 (7%) of 1761 patients who received the switch strategy and 128 (7%) of 1766 patients who received upfront treatment. Grade 1 musculoskeletal events were more frequent with the upfront schedule than with the switch schedule (924 [52%] of 1766 patients vs 745 [42%] of 1761 patients). All other grade 3–4 adverse events occurred in less than 2% of patients in either group. Interpretation: 5 years of treatment with aromatase inhibitors was not superior to 2 years of tamoxifen followed by 3 years of aromatase inhibitors. None of the three aromatase inhibitors was superior to the others in terms of efficacy. Therefore, patient preference, tolerability, and financial constraints should be considered when deciding the optimal treatment approach in this setting. Funding: Italian Drug Agency.

Published
2018

7. PANHER study: a 20-year treatment outcome analysis from a multicentre observational study of HER2-positive advanced breast cancer patients from the real-world setting

Author

Angela Maione, Nicola Tinari, Paola Pinnarò, Enzo Maria Ruggeri, Isabella Sperduti, Olivia Bacciu, Emanuela Risi, Icro Meattini, Federica Tomao, Luca Marchetti, Nicola D’Ostilio, Patrizia Vici, Lorenza Landi, Giuseppina Sarobba, Lucia Mentuccia, Elisabetta Landucci, Emilio Bria, A.F. Scinto, Gennaro Ciliberto, Laura Pizzuti, Elena Fiorio, Andrea Michelotti, Ida Paris, Simonetta Stani, Antonio Russo, Clara Natoli, Rosa Saltarelli, Alessandra Cassano, Paolo Marchetti, Maria Agnese Fabbri, Daniele Marinelli, Ferdinando Riccardi, Mauro Minelli, Corrado Ficorella, Anna Ceribelli, Maria Rosaria Valerio, Maddalena Barba, Jennifer Foglietta, Maria Mauri, Teresa Gamucci, Luca Moscetti, Beatrice Taurelli Salimbeni, Fabio Pelle, Daniele Santini, Andrea Botticelli, Vito Lorusso, Mirco Pistelli, Giacomo Barchiesi, Francesco Giotta, Eriseld Krasniqi, Antonino Grassadonia, Simone Scagnoli, Valentina Sini, Katia Cannita, Flavia Cavicchi, Michele De Tursi, Mimma Raffaele, Marco Mazzotta, Sonia Cappelli, Paola Scavina, Francesca Sofia Di Lisa, Giuliana D’Auria, Armando Orlandi, Marcello Maugeri-Saccà, Federico Cappuzzo, Claudio Botti, Nello Salesi, Lorenzo Livi, Beatrice Fratini, Giulia Bon, Silverio Tomao, Giuseppe Sanguineti, Enzo Veltri, Domenico Corsi, Enrico Cortesi, Rossana Berardi, Laura Iezzi, Rosalinda Rossi, Giuseppe Tonini, Elisabetta Maria Capomolla, Pizzuti L., Krasniqi E., Sperduti I., Barba M., Gamucci T., Mauri M., Veltri E.M., Meattini I., Berardi R., Di Lisa F.S., Natoli C., Pistelli M., Iezzi L., Risi E., D'Ostilio N., Tomao S., Ficorella C., Cannita K., Riccardi F., Cassano A., Bria E., Fabbri M.A., Mazzotta M., Barchiesi G., Botticelli A., D'Auria G., Ceribelli A., Michelotti A., Russo A., Salimbeni B.T., Sarobba G., Giotta F., Paris I., Saltarelli R., Marinelli D., Corsi D., Capomolla E.M., Sini V., Moscetti L., Mentuccia L., Tonini G., Raffaele M., Marchetti L., Minelli M., Ruggeri E.M., Scavina P., Bacciu O., Salesi N., Livi L., Tinari N., Grassadonia A., Fedele Scinto A., Rossi R., Valerio M.R., Landucci E., Stani S., Fratini B., Maugeri-Sacca M., De Tursi M., Maione A., Santini D., Orlandi A., Lorusso V., Cortesi E., Sanguineti G., Pinnaro P., Cappuzzo F., Landi L., Botti C., Tomao F., Cappelli S., Bon G., Pelle F., Cavicchi F., Fiorio E., Foglietta J., Scagnoli S., Marchetti P., Ciliberto G., and Vici P.

Subjects
Oncology, medicine.medical_specialty, Advanced breast, T-DM1, Treatment outcome, Lapatinib, Breast cancer, pertuzumab, Internal medicine, Medicine, lapatinib, RC254-282, advanced breast cancer, business.industry, Human epidermal growth factor, HER2-positive, sequence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cancer, medicine.disease, Observational study, Pertuzumab, business, medicine.drug
Abstract

Background: The evolution of therapeutic landscape of human epidermal growth factor receptor-2 (HER2)-positive breast cancer (BC) has led to an unprecedented outcome improvement, even if the optimal sequence strategy is still debated. To address this issue and to provide a picture of the advancement of anti-HER2 treatments, we performed a large, multicenter, retrospective study of HER2-positive BC patients. Methods: The observational PANHER study included 1,328 HER2-positive advanced BC patients treated with HER2 blocking agents since June 2000 throughout July 2020. Endpoints of efficacy were progression-free survival (PFS) and overall survival (OS). Results: Patients who received a first-line pertuzumab-based regimen showed better PFS ( p < 0.0001) and OS ( p = 0.004) than those receiving other treatments. Median PFS and mOS from second-line starting were 8 and 28 months, without significant differences among various regimens. Pertuzumab-pretreated patients showed a mPFS and a mOS from second-line starting not significantly affected by type of second line, that is, T-DM1 or lapatinib/capecitabine ( p = 0.80 and p = 0.45, respectively). Conversely, pertuzumab-naïve patients receiving second-line T-DM1 showed a significantly higher mPFS compared with that of patients treated with lapatinib/capecitabine ( p = 0.004). Median OS from metastatic disease diagnosis was higher in patients treated with trastuzumab-based first line followed by second-line T-DM1 in comparison to pertuzumab-based first-line and second-line T-DM1 ( p = 0.003), although these data might be partially influenced by more favorable prognostic characteristics of patients in the pre-pertuzumab era. No significant differences emerged when comparing patients treated with ‘old’ or ‘new’ drugs ( p = 0.43), even though differences in the length of the follow-up between the two cohorts should be taken into account. Conclusion: Our results confirmed a relevant impact of first-line pertuzumab-based treatment and showed lower efficacy of second-line T-DM1 in trastuzumab/pertuzumab pretreated, as compared with pertuzumab-naïve patients. Our findings may help delineate a more appropriate therapeutic strategy in HER2-positive metastatic BC. Prospective randomized trials addressing this topic are awaited.

Published
2021

8. Prognostic Relevance of Neutrophil to Lymphocyte Ratio (NLR) in Luminal Breast Cancer: A Retrospective Analysis in the Neoadjuvant Setting

Author

Marco Mazzotta, Nicola Tinari, Eriseld Krasniqi, Laura Iezzi, A. Amodio, Clara Natoli, Laura Pizzuti, Giuseppe Cicero, Maddalena Barba, Vincenzo Graziano, Patrizia Vici, Antonino Grassadonia, Daniele Marinelli, Grassadonia A., Graziano V., Iezzi L., Vici P., Barba M., Pizzuti L., Cicero G., Krasniqi E., Mazzotta M., Marinelli D., Amodio A., Natoli C., Tinari N., Graziano, Vincenzo [0000-0001-7656-824X], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Oncology, Adult, medicine.medical_specialty, Multivariate analysis, Neutrophils, QH301-705.5, medicine.medical_treatment, Breast Neoplasms, Article, Disease-Free Survival, predictive/prognostic biomarkers, 03 medical and health sciences, 0302 clinical medicine, Text mining, Breast cancer, luminal breast cancer, Internal medicine, Medicine, Humans, Lymphocytes, Neutrophil to lymphocyte ratio, Biology (General), Neoadjuvant therapy, Aged, Retrospective Studies, Chemotherapy, business.industry, Proportional hazards model, allergology, fungi, Luminal breast cancer, Neoadjuvant chemotherapy, Neutrophil to lymphocyte ratio (NLR), Predictive/prognostic biomarkers, Female, Ki-67 Antigen, Middle Aged, Multivariate Analysis, Prognosis, Treatment Outcome, Neoadjuvant Therapy, Histology, General Medicine, medicine.disease, neutrophil to lymphocyte ratio (NLR), 030104 developmental biology, 030220 oncology & carcinogenesis, Population study, business, neoadjuvant chemotherapy
Abstract

The neutrophil to lymphocyte ratio (NLR) is a promising predictive and prognostic factor in breast cancer. We investigated its ability to predict disease-free survival (DFS) and overall survival (OS) in patients with luminal A- or luminal B-HER2-negative breast cancer who received neoadjuvant chemotherapy (NACT). Pre-treatment complete blood cell counts from 168 consecutive patients with luminal breast cancer were evaluated to assess NLR. The study population was stratified into NLRlow or NLRhigh according to a cut-off value established by receiving operator curve (ROC) analysis. Data on additional pre- and post-treatment clinical-pathological characteristics were also collected. Kaplan–Meier curves, log-rank tests, and Cox proportional hazards models were used for statistical analyses. Patients with pre-treatment NLRlow showed a significantly shorter DFS (HR: 6.97, 95% CI: 1.65–10.55, p = 0.002) and OS (HR: 7.79, 95% CI: 1.25–15.07, p = 0.021) compared to those with NLRhigh. Non-ductal histology, luminal B subtype, and post-treatment Ki67 ≥ 14% were also associated with worse DFS (p = 0.016, p = 0.002, and p = 0.001, respectively). In a multivariate analysis, luminal B subtype, post-treatment Ki67 ≥ 14%, and NLRlow remained independent prognostic factors for DFS, while only post-treatment Ki67 ≥ 14% and NLRlow affected OS. The present study provides evidence that pre-treatment NLRlow helps identify women at higher risk of recurrence and death among patients affected by luminal breast cancer treated with NACT.

Published
2021

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

Author

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

Subjects
0301 basic medicine, Oncology, Physiology, Receptor, ErbB-2, Clinical Biochemistry, Ado-Trastuzumab Emtansine, Settore MED/06, body mass index, HER2-positive metastatic breast cancer, pertuzumab, trastuzumab emtansine, chemistry.chemical_compound, 0302 clinical medicine, Antineoplastic Agents, Immunological, Aged, 80 and over, education.field_of_study, Univariate analysis, Middle Aged, Metastatic breast cancer, Progression-Free Survival, Quartile, 030220 oncology & carcinogenesis, Disease Progression, Female, Pertuzumab, medicine.drug, Adult, medicine.medical_specialty, Population, Breast Neoplasms, Antibodies, Monoclonal, Humanized, 03 medical and health sciences, Breast cancer, Settore MED/04 - PATOLOGIA GENERALE, Internal medicine, medicine, Humans, Obesity, education, Aged, business.industry, nutritional and metabolic diseases, Cell Biology, Overweight, medicine.disease, 030104 developmental biology, chemistry, Trastuzumab emtansine, MED/06 - ONCOLOGIA MEDICA, business, Body mass index
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

10. 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

Isacco Desideri, G. Tonini, Emanuela Magnolfi, L. Pizzuti, Jennifer Foglietta, Marina Elena Cazzaniga, Adamo, Patrizia Vici, Enrico Cortesi, Emanuela Risi, G. D'Auria, Loretta D'Onofrio, Mario Roselli, Isabella Sperduti, N. Tinari, Nicola D’Ostilio, A. Vaccaro, Icro Meattini, Federica Tomao, Giacomo Barchiesi, B Di Cocco, F Cardillo, Enzo Veltri, Claudia Omarini, Mirco Pistelli, Clara Natoli, Carlo Garufi, E. Landucci, M. Mauri, Rosanna Mirabelli, Federico Piacentini, Domenico Corsi, A.F. Scinto, Alice Villa, Alain Gelibter, C. De Angelis, Marco Mazzotta, Gennaro Ciliberto, Claudio Zamagni, Giuseppe Sanguineti, Fiorentino Izzo, Elizabeth H. Baldini, Rossana Berardi, Grr Ricciardi, Maddalena Barba, Ornella Garrone, Ida Paris, Luisa Carbognin, A. Botticelli, Giuseppina Sarobba, Silverio Tomao, Antonio Astone, Lucia Mentuccia, P Del Medico, Lorusso, Daniele Santini, M. Della Giulia, Riccardo Samaritani, Francesco Giotta, Alessandra Cassano, Laura Iezzi, Maria Agnese Fabbri, R De Maria, Eriseld Krasniqi, Raffaele Giusti, Sini, Lorenzo Livi, Ernesto Rossi, Andrea Michelotti, Emilio Bria, A Di Leo, Luca Moscetti, Corrado Ficorella, Antonino Grassadonia, Roberta Sarmiento, Katia Cannita, Filippo Greco, Sandro Barni, Elena Fiorio, Teresa Gamucci, Magri, Antonio Russo, M. De Tursi, N. La Verde, Daniele Generali, Paolo Marchetti, 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, and Vici, P

Subjects
Oncology, Cancer Research, Multivariate analysis, Settore MED/06 - Oncologia Medica, Receptor, ErbB-2, T-DM1, Estrogen receptor, 0302 clinical medicine, ErbB-2, Trastuzumab, Receptors, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Molecular Targeted Therapy, Neoplasm Metastasis, Cancer Therapy and Prevention, Progesterone, Aged, 80 and over, advanced breast cancer, Tumor, real world, Middle Aged, Prognosis, Metastatic breast cancer, Immunohistochemistry, Gene Expression Regulation, Neoplastic, trastuzumab, Receptors, Estrogen, 030220 oncology & carcinogenesis, Female, HER2 positive, pertuzumab, Adult, Aged, Biomarkers, Tumor, Breast Neoplasms, Humans, Neoplasm Staging, Receptors, Progesterone, Pertuzumab, medicine.drug, Receptor, medicine.medical_specialty, T‐DM1, chemotherapy, 03 medical and health sciences, Breast cancer, Settore MED/04 - PATOLOGIA GENERALE, Internal medicine, medicine, Neoplastic, business.industry, medicine.disease, Estrogen, Settore CHIM/08 - Chimica Farmaceutica, Gene Expression Regulation, MED/06 - ONCOLOGIA MEDICA, business, Biomarkers, Hormone
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., What's new? About half of breast cancers positive for human epidermal growth factor (HER2) also express hormone receptors but the impact of hormone receptor status on the success of HER2‐directed treatments is not fully explored. Here the authors retrospectively assessed tumor behavior and treatment outcomes in 738 women with HER2+ metastatic breast cancer treated with new generation anti‐HER2 agents. Distinct hormone receptor expression patterns significantly affected the progression free and overall survival, justifying further studies to define optimal treatment regimens and the interplay between hormone receptor and HER2 signaling.

Published
2020

11. Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score

Author

Marta Peri, Sergio Rizzo, Luciana Irtelli, Antonio Russo, Viviana Bazan, Antonino Grassadonia, Valerio Gristina, Michele De Tursi, Marta Castiglia, Nadia Barraco, Antonio Galvano, A. Guarini, Clara Natoli, Alessandro Bertani, Galvano A., Peri M., Guarini A.A., Castiglia M., Grassadonia A., De Tursi M., Irtelli L., Rizzo S., Bertani A., Gristina V., Barraco N., Russo A., Natoli C., and Bazan V.

Subjects
Oncology, medicine.medical_specialty, Lung, Blood based biomarkers, business.industry, Settore MED/06 - Oncologia Medica, small-cell lung cancer (SCLC), systemic inflammatory response, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Inflammatory biomarkers, lcsh:RC254-282, Neuroendocrine Carcinomas, medicine.anatomical_structure, Internal medicine, medicine, Prognostic biomarker, Neuroendocrine carcinoma, Original Article, business, predictive biomarker, prognostic biomarker, neuroendocrine tumor, Predictive biomarker, blood-based biomarker
Abstract

Background: Lung neuroendocrine carcinoma (NEC) is characterized by aggressive clinical behavior and lack of treatment advances. We evaluate the prognostic and the predictive roles of systemic inflammatory biomarkers in patient circulating blood: neutrophil–lymphocyte ratio (NLR), lactate dehydrogenase (LDH), advanced lung cancer inflammation index (ALI), and the Lung Immune Prognostic Index (LIPI) score. Methods: A total of 120 patients with small-cell lung cancer (SCLC) ( n = 110) and large cell neuroendocrine carcinoma (LCNEC) ( n = 10) were enrolled. Overall survival (OS) was evaluated by Kaplan–Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS while χ2 test was used for categorical data. Results: NLR cutoff value was 1.93. NLR was measured before and after first-line chemotherapy; 25 (21%) patients had higher NLR (delta NLR >1), whereas NLR was lower in 37 (31%). At the univariate analysis, median OS was 12 months: OS for SCLC and LCNEC were 11 months and 14 months, respectively. OS had a prognostic positive value in patients with pre-treatment NLR 1.93) had an increased probability of tumor progression ( p = 0.045, χ2 test). Conclusion: This study demonstrated that systemic inflammatory biomarkers could facilitate the understanding of survival differences in the clinical management of lung NEC patients, underlying the need for prospective biomarker-driven studies in the immune checkpoint inhibitors setting.

Published
2020

12. 'Back to a false normality': new intriguing mechanisms of resistance to PARP inhibitors

Author

Nadia Barraco, Valentina Calò, Sergio Rizzo, Angela Listì, Antonio Russo, Lorena Incorvaia, Viviana Bazan, Antonio Galvano, Marcello Ciaccio, Clara Natoli, Francesc Passiglia, R. Maragliano, Incorvaia, L., Passiglia, F., Rizzo, S., Galvano, A., Listì, A., Barraco, N., Maragliano, R., Calò, V., Natoli, C., Ciaccio, M., Bazan, V., and Russo, A.

Subjects
0301 basic medicine, Poly ADP ribose polymerase, medicine.medical_treatment, Review, Synthetic lethality, Poly(ADP-ribose) Polymerase Inhibitors, medicine.disease_cause, Poly (ADP-Ribose) Polymerase Inhibitor, resistance, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Cell Line, Tumor, BRCA1-2, Animals, Humans, Medicine, PARP inhibitors, BRCA2 Protein, Genetics, Mutation, Chemotherapy, BRCA1 Protein, business.industry, Resistance, Oncology, medicine.disease, Clinical trial, PARP inhibitor, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Cancer research, business
Abstract

Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recently clinical studies of PARP-inhibitors have been extended across different tumor types harboring BRCA-mutations, including also "BRCA-like" sporadic tumors with homologous recombination deficiency (HRD). This review summarizes the biological background underlying PARP-inhibition, reporting the results of the most relevant clinical trials carried out in patients treated with PARP inhibitors alone or in combination with chemotherapy. Molecular mechanisms responsible for the occurrence of both primary and acquired resistance have been elucidated, in order to support the development of new treatment strategies.

Published
2016

13. Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation

Author

Laura Pierdomenico, Clara Natoli, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, Paola Lanuti, Fausta Ciccocioppo, Davide Brocco, I. G. Rapposelli, Vincenzo Graziano, P. Del Boccio, Maria Concetta Cufaro, Eva Ercolino, Marta Peri, Giuseppina Bologna, Paola Simeone, Marco Marchisio, Antonino Grassadonia, M. De Tursi, P. Di Marino, Grassadonia, A [0000-0002-2459-0661], Del Boccio, P [0000-0003-1653-2194], Marchisio, M [0000-0003-3058-3422], Natoli, C [0000-0001-7295-0230], and Apollo - University of Cambridge Repository

Subjects
Oncology, CD31, medicine.medical_specialty, Article Subject, 32 Biomedical and Clinical Sciences, Proteomics, lcsh:RC254-282, Flow cytometry, Clinical Research, Cancer stem cell, Internal medicine, medicine, 2.1 Biological and endogenous factors, Cancer, 2 Aetiology, medicine.diagnostic_test, business.industry, Prevention, Cell sorting, 3211 Oncology and Carcinogenesis, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Precision medicine, medicine.disease, 4.1 Discovery and preclinical testing of markers and technologies, Biomarker (medicine), 4 Detection, screening and diagnosis, business, Research Article, 4.2 Evaluation of markers and technologies
Abstract

The recent introduction of the “precision medicine” concept in oncology pushed cancer research to focus on dynamic measurable biomarkers able to predict responses to novel anticancer therapies in order to improve clinical outcomes. Recently, the involvement of extracellular vesicles (EVs) in cancer pathophysiology has been described, and given their release from all cell types under specific stimuli, EVs have also been proposed as potential biomarkers in cancer. Among the techniques used to study EVs, flow cytometry has a high clinical potential. Here, we have applied a recently developed and simplified flow cytometry method for circulating EV enumeration, subtyping, and isolation from a large cohort of metastatic and locally advanced nonhaematological cancer patients (N = 106); samples from gender- and age-matched healthy volunteers were also analysed. A large spectrum of cancer-related markers was used to analyse differences in terms of peripheral blood circulating EV phenotypes between patients and healthy volunteers, as well as their correlation to clinical outcomes. Finally, EVs from patients and controls were isolated by fluorescence-activated cell sorting, and their protein cargoes were analysed by proteomics. Results demonstrated that EV counts were significantly higher in cancer patients than in healthy volunteers, as previously reported. More interestingly, results also demonstrated that cancer patients presented higher concentrations of circulating CD31+ endothelial-derived and tumour cancer stem cell-derived CD133 + CD326- EVs, when compared to healthy volunteers. Furthermore, higher levels of CD133 + CD326− EVs showed a significant correlation with a poor overall survival. Additionally, proteomics analysis of EV cargoes demonstrated disparities in terms of protein content and function between circulating EVs in cancer patients and healthy controls. Overall, our data strongly suggest that blood circulating cancer stem cell-derived EVs may have a role as a diagnostic and prognostic biomarker in cancer.

Published
2019

14. Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations

Author

Angelo Delmonte, Francesco Passiglia, Diana Giannarelli, Paolo Bidoli, Lorenzo Livi, G. Puppo, Francesco Gelsomino, Giovanna Finocchiaro, Domenico Galetta, Olga Martelli, Oscar Alabiso, Rita Chiari, Daniele Turci, Enrico Ricevuto, Guido Francini, Alfonso Illiano, Elisa Roca, Anna Cecilia Bettini, Clara Natoli, Federico Cappuzzo, Monica Giordano, C. Defferrari, Passiglia, F, Cappuzzo, F, Alabiso, O, Bettini, A, Bidoli, P, Chiari, R, Defferrari, C, Delmonte, A, Finocchiaro, G, Francini, G, Gelsomino, F, Giannarelli, D, Giordano, M, Illiano, A, Livi, L, Martelli, O, Natoli, C, Puppo, G, Ricevuto, E, Roca, E, Turci, D, and Galetta, D

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Cancer Research, medicine.disease_cause, Predictive markers, Article, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Carcinoma, Non-Small-Cell Lung, medicine, Carcinoma, 80 and over, Humans, Progression-free survival, Lung cancer, Non-Small-Cell Lung, neoplasms, Aged, Aged, 80 and over, business.industry, Cancer, Common Terminology Criteria for Adverse Events, Middle Aged, medicine.disease, digestive system diseases, Progression-Free Survival, respiratory tract diseases, Nivolumab, Female, Mutation, Immunotherapy, 030220 oncology & carcinogenesis, Expanded access, KRAS, business, Non-small-cell lung cancer
Abstract

Background: The present study investigated the efficacy and safety of nivolumab in pre-treated patients with advanced NSCLC harbouring KRAS mutations. Methods: Clinical data and KRAS mutational status were analysed in patients treated with nivolumab within the Italian Expanded Access Program. Objective response rate, progression-free survival and overall survival were evaluated. Patients were monitored for adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events. Results: Among 530 patients evaluated for KRAS mutations, 206 (39%) were positive while 324 (61%) were KRAS wild-type mutations. KRAS status did not influence nivolumab efficacy in terms of ORR (20% vs 17%, P = 0.39) and DCR (47% vs 41%, P = 0.23). The median PFS and OS were 4 vs 3 months (P = 0.5) and 11.2 vs 10 months (P = 0.8) in the KRAS-positive vs the KRAS-negative group. The 3-months PFS rate was significantly higher in the KRAS-positive group as compared to the KRAS-negative group (53% vs 42%, P = 0.01). The percentage of any grade and grade 3–4 AEs were 45% vs 33% (P = 0.003) and 11% vs 6% (P = 0.03) in KRAS-positive and KRAS-negative groups, respectively. Conclusions: Nivolumab is an effective and safe treatment option for patients with previously treated, advanced non-squamous NSCLC regardless of KRAS mutations.

Published
2019

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

Author

Michele De Tursi, Marco Mazzotta, Armando Orlandi, Marina Elena Cazzaniga, Enrico Cortesi, Maddalena Barba, Laura Iezzi, Giuseppe Tonini, E. Landucci, Lucio Laudadio, Domenico Sergi, Alessandra Cassano, Giuseppe Sanguineti, Nicla La Verde, Riccardo Samaritani, Patrizia Seminara, Antonio Russo, Claudio Zamagni, Simone Scagnoli, Valentina Magri, Ramy Kayal, Enzo Veltri, Francesca Aroldi, Clara Natoli, Ilaria Portarena, Samantha Forciniti, Laura Ferrari, Lucia Mentuccia, Gennaro Ciliberto, Daniele Santini, Teresa Gamucci, Filippo Greco, Silvia Carpano, Mario Roselli, Sandro Barni, A. Fabbri, Isabella Sperduti, A. Vaccaro, Ida Paris, Daniela Rubino, Ruggero De Maria, Patrizia Vici, Claudia De Angelis, Giulia Pomati, Luisa Carbognin, Simona Vallarelli, Antonino Grassadonia, Mirco Pistelli, A.F. Scinto, Katia Cannita, Andrea Michelotti, Domenico Corsi, E. Capomolla, Corrado Ficorella, Nicola Tinari, Vito Lorusso, Rossana Berardi, Andrea Botticelli, Antonio Giordano, Silverio Tomao, Laura Pizzuti, Paolo Marchetti, Maria Giuseppina Sarobba, Valentina Sini, Luca Moscetti, Lucrezia Diodati, Maria Vincenza Mancini, Luciano Mariani, 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, Laura, Giordano, Antonio, Michelotti, Andrea, Mazzotta, Marco, Natoli, Clara, Gamucci, Teresa, De Angelis, Claudia, Landucci, Elisabetta, Diodati, Lucrezia, Iezzi, Laura, Mentuccia, Lucia, Fabbri, Agnese, Barba, Maddalena, Sanguineti, Giuseppe, Marchetti, Paolo, Tomao, Silverio, Mariani, Luciano, Paris, Ida, Lorusso, Vito, Vallarelli, Simona, Cassano, Alessandra, Airoldi, Francesca, Orlandi, Armando, Moscetti, Luca, Sergi, Domenico, Sarobba, Maria Giuseppina, Tonini, Giuseppe, Santini, Daniele, Sini, Valentina, Veltri, Enzo, Vaccaro, Angela, Ferrari, Laura, De Tursi, Michele, Tinari, Nicola, Grassadonia, Antonino, Greco, Filippo, Botticelli, Andrea, La Verde, Nicla, Zamagni, Claudio, Rubino, Daniela, Cortesi, Enrico, Magri, Valentina, Pomati, Giulia, Scagnoli, Simone, Capomolla, Elisabetta, Kayal, Ramy, Scinto, Angelo Fedele, Corsi, Domenico, Cazzaniga, Marina, Laudadio, Lucio, Forciniti, Samantha, Mancini, Maria, Carbognin, Luisa, Seminara, Patrizia, Barni, Sandro, Samaritani, Riccardo, Roselli, Mario, Portarena, Ilaria, Russo, Antonio, Ficorella, Corrado, Cannita, Katia, Carpano, Silvia, Pistelli, Mirco, Berardi, Rossana, De Maria, Ruggero, Sperduti, Isabella, Ciliberto, Gennaro, and Vici, Patrizia

Subjects
Male, 0301 basic medicine, Oncology, Pyridines, Receptor, ErbB-2, Physiology, Clinical Biochemistry, Piperazines, chemistry.chemical_compound, 0302 clinical medicine, Exemestane, Antineoplastic Combined Chemotherapy Protocols, advanced breast cancer, hormonal therapy, endocrine resistance, palbociclib, real-world setting, Breast, Aged, 80 and over, advanced breast cancer, hormonal therapy, Middle Aged, Treatment Outcome, Receptors, Estrogen, 030220 oncology & carcinogenesis, Toxicity, Female, Receptors, Progesterone, medicine.drug, Adult, Cell Biology, medicine.medical_specialty, Breast Neoplasms, Palbociclib, Neutropenia, Disease-Free Survival, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, Everolimus, Settore MED/06 - ONCOLOGIA MEDICA, business.industry, Cancer, medicine.disease, Confidence interval, 030104 developmental biology, chemistry, MED/06 - ONCOLOGIA MEDICA, business, Hormone
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

16. A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: When overweight becomes favorable

Author

Mario Occhipinti, Gian Carlo Antonini Cappellini, Marco Filetti, Giampiero Porzio, Clara Natoli, Andrea De Giglio, Francesca Rastelli, Federica Zoratto, Silvia Rinaldi, Cecilia Anesi, Sebastiano Buti, Rita Chiari, Fabiana Perrone, Francesco Atzori, Pietro Di Marino, Andrea Botticelli, Enzo Veltri, Melissa Bersanelli, Federica Pergolesi, Nicola Tinari, Alessio Cortellini, Paolo A. Ascierto, Corrado Ficorella, Daniele Santini, Alain Gelibter, Marianna Tudini, Rossana Berardi, Maria Concetta Fargnoli, Tea Zeppola, Rosa Rita Silva, Marcello Tiseo, Riccardo Marconcini, Daniela Iacono, Raffaele Giusti, Federica De Galitiis, Annagrazia Pireddu, Paolo Marchetti, Alessandro Parisi, Francesco Malorgio, Maria Giuseppa Vitale, Michele De Tursi, Maria Michiara, Marco Russano, Biagio Ricciuti, Katia Cannita, Cortellini A., Bersanelli M., Buti S., Cannita K., Santini D., Perrone F., Giusti R., Tiseo M., Michiara M., Di Marino P., Tinari N., De Tursi M., Zoratto F., Veltri E., Marconcini R., Malorgio F., Russano M., Anesi C., Zeppola T., Filetti M., Marchetti P., Botticelli A., Antonini Cappellini G.C., De Galitiis F., Vitale M.G., Rastelli F., Pergolesi F., Berardi R., Rinaldi S., Tudini M., Silva R.R., Pireddu A., Atzori F., Chiari R., Ricciuti B., De Giglio A., Iacono D., Gelibter A., Occhipinti M.A., Parisi A., Porzio G., Fargnoli M.C., Ascierto P.A., Ficorella C., and Natoli C.

Subjects
Male, 0301 basic medicine, Cancer Research, Programmed Cell Death 1 Receptor, Kaplan-Meier Estimate, Anti-PD-1/PD-L1, Overweight, Gastroenterology, B7-H1 Antigen, Body Mass Index, Antineoplastic Agents, Immunological, 0302 clinical medicine, BMI, Cancer, Immunotherapy, Obesity, Immunology and Allergy, Immunology, Molecular Medicine, Oncology, Pharmacology, Renal cell carcinoma, Neoplasms, Molecular Targeted Therapy, Aged, 80 and over, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Underweight, medicine.symptom, Research Article, Adult, medicine.medical_specialty, lcsh:RC254-282, Young Adult, 03 medical and health sciences, Internal medicine, Biomarkers, Tumor, medicine, Humans, Aged, Neoplasm Staging, Proportional Hazards Models, business.industry, nutritional and metabolic diseases, Retrospective cohort study, medicine.disease, Clinical trial, 030104 developmental biology, business, Body mass index
Abstract

Background Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. Patients and methods We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (

Published
2019

17. Corrigendum to 'Circulating Cancer Stem Cell-Derived Extracellular Vesicles as a Novel Biomarker for Clinical Outcome Evaluation'

Author

Paola Lanuti, Maria Concetta Cufaro, P. Di Marino, P. Del Boccio, Antonino Grassadonia, Giuseppina Bologna, Marco Marchisio, Marta Peri, I. G. Rapposelli, Clara Natoli, Vincenzo Graziano, Laura Pierdomenico, Davide Brocco, Fausta Ciccocioppo, Paola Simeone, Sebastiano Miscia, Nicola Tinari, Damiana Pieragostino, M. De Tursi, Eva Ercolino, Grassadonia, A [0000-0002-2459-0661], Del Boccio, P [0000-0003-1653-2194], Marchisio, M [0000-0003-3058-3422], Natoli, C [0000-0001-7295-0230], and Apollo - University of Cambridge Repository

Subjects
business.industry, education, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 32 Biomedical and Clinical Sciences, 3211 Oncology and Carcinogenesis, Extracellular vesicles, Oncology, Cancer stem cell, Cancer research, Biomarker (medicine), Medicine, Corrigendum, business, RC254-282
Abstract

[This corrects the article DOI: 10.1155/2019/5879616.].

Published
2020

18. What links BRAF to the heart function? new insights from the cardiotoxicity of BRAF inhibitors in cancer treatment

Author

Viviana Bazan, Giuseppe Lo Re, Fabrizio Bronte, Giuseppe Bronte, Clara Natoli, Salvatore Novo, Antonio Russo, Enrico Bronte, M.G. Bavetta, Giuseppina Novo, Giuseppe Brancatelli, Bronte, E., Bronte, G., Novo, G., Bronte, F., Bavetta, M., Re, G., Brancatelli, G., Bazan, V., Natoli, C., Novo, S., and Russo, A.

Subjects
Sorafenib, Proto-Oncogene Proteins B-raf, B-RAF inhibitors, cardio-oncology, Skin Neoplasms, cardiotoxicity, Antineoplastic Agents, Review, B-RAF inhibitor, Pharmacology, QT interval, Sudden cardiac death, chemistry.chemical_compound, Regorafenib, medicine, Animals, Humans, Molecular Targeted Therapy, dabrafenib, Vemurafenib, Melanoma, Protein Kinase Inhibitors, Cardiotoxicity, Clinical Trials as Topic, business.industry, B-RAF, Dabrafenib, Arrhythmias, Cardiac, Heart, medicine.disease, Oncology, chemistry, Cancer research, business, medicine.drug, Signal Transduction
Abstract

The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation.

Published
2015

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

Author

Vici, Patrizia, Pizzuti, Laura, Michelotti, Andrea, Sperduti, Isabella, Natoli, Clara, Mentuccia, Lucia, Di Lauro, Luigi, Sergi, Domenico, Marchetti, Paolo, Santini, Daniele, Magnolfi, Emanuela, Iezzi, Laura, Moscetti, Luca, Fabbri, Agnese, Cassano, Alessandra, Grassadonia, Antonino, Omarini, Claudia, Piacentini, Federico, Botticelli, Andrea, Bertolini, Ilaria, Scinto, Angelo Fedele, Zampa, Germano, Mauri, Maria, D'Onofrio, Loretta, Sini, Valentina, Barba, Maddalena, Maugeri-saccã&nbsp, Marcello, Rossi, Ernesto, Landucci, Elisabetta, Tomao, Silverio, Alberti, Antonio Maria, Giotta, Francesco, Ficorella, Corrado, Adamo, Vincenzo, Russo, Antonio, Lorusso, Vito, Cannita, Katia, Barni, Sandro, Laudadio, Lucio, Greco, Filippo, Garrone, Ornella, Della Giulia, Marina, Marolla, Paolo, Sanguineti, Giuseppe, Di Cocco, Barbara, Ciliberto, Gennaro, De Maria, Ruggero, Gamucci, Teresa, Vici, P., Pizzuti, L., Michelotti, A., Sperduti, I., Natoli, C., Mentuccia, L., Di Lauro, L., Sergi, D., Marchetti, P., Santini, D., Magnolfi, E., Iezzi, L., Moscetti, L., Fabbri, A., Cassano, A., Grassadonia, A., Omarini, C., Piacentini, F., Botticelli, A., Bertolini, I., Scinto, A., Zampa, G., Mauri, M., D'Onofrio, L., Sini, V., Barba, M., Maugeri-Saccà , M., Rossi, E., Landucci, E., Tomao, S., Alberti, A., Giotta, F., Ficorella, C., Adamo, V., Russo, A., Lorusso, V., Cannita, K., Barni, S., Laudadio, L., Greco, F., Garrone, O., Della Giulia, M., Marolla, P., Sanguineti, G., Di Cocco, B., Ciliberto, G., De Maria, R., and Gamucci, T.

Subjects
0301 basic medicine, Oncology, HER2 positive, real-world, medicine.medical_specialty, T-DM1, metastatic breast cancer, previous pertuzumab, Metastatic breast cancer, Previous pertuzumab, Real-world, oncology, ECOG Performance Status, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Settore MED/04 - PATOLOGIA GENERALE, law, Internal medicine, Medicine, Univariate analysis, Settore MED/06 - ONCOLOGIA MEDICA, business.industry, Cancer, medicine.disease, Log-rank test, trastuzumab, 030104 developmental biology, chemistry, Trastuzumab emtansine, 030220 oncology & carcinogenesis, HER2 positive, Metastatic breast cancer, Previous pertuzumab, Real-world, T-DM1, Oncology, Pertuzumab, business, medicine.drug, Research Paper
Abstract

We addressed trastuzumab emtansine (T-DM1) efficacy 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 significant 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 benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences 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 benefit (p < 0.0001), while overall survival was positively affected by lower ECOG PS (p < 0.0001), absence of brain metastases (p 0.05), and clinical benefit (p < 0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order.

Published
2017

20. Fulvestrant (FUL) as first-line therapy in HR+ve, HER2-ve advanced breast cancer (ABC) patients (pts): when clinical practice comes earlier than clinical trials. Results from the GIM-13 AMBRA study

Author

L. Del Mastro, Filippo Montemurro, Giorgio Mustacchi, M. De Laurentiis, Lorenzo Livi, Clara Natoli, Andrea Michelotti, Michela Donadio, Monica Giordano, Emanuela Romagnoli, Piero Marchetti, Laura Biganzoli, F. Riccardi, Paolo Pronzato, A. Turletti, S. De Placido, Ornella Garrone, Marina Elena Cazzaniga, Pronzato, P, Mustacchi, G, Riccardi, F, Turletti, A, Michelotti, A, Natoli, C, Livi, L, Del Mastro, L, Donadio, M, Garrone, O, Giordano, M, De Laurentiis, M, Marchetti, P, Montemurro, F, Romagnoli, E, De Placido, S, Biganzoli, L, and Cazzaniga, M

Subjects
Oncology, Gynecology, medicine.medical_specialty, Fulvestrant, business.industry, Advanced breast, Cancer, Hematology, medicine.disease, Clinical Practice, Clinical trial, First line therapy, breast cancer, Internal medicine, medicine, MED/06 - ONCOLOGIA MEDICA, business, medicine.drug
Published
2017

21. The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?

Author

Antonio Galvano, Sergio Rizzo, Daniele Fanale, Fabio Rizzo, Lorena Incorvaia, Christian Rolfo, Angela Listì, Viviana Bazan, Francesco Passiglia, Clara Natoli, Giuseppe Bronte, Antonio Russo, Bronte, G., Incorvaia, L., Rizzo, S., Passiglia, F., Galvano, A., Rizzo, F., Rolfo, C., Fanale, D., Listì, A., Natoli, C., Bazan, V., and Russo, A.

Subjects
0301 basic medicine, Oncology, Drug, Mesothelioma, medicine.medical_specialty, Pathology, Lung Neoplasms, Settore MED/06 - Oncologia Medica, media_common.quotation_subject, medicine.medical_treatment, Pleural Neoplasms, Resistance, Antineoplastic Agents, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Animals, Humans, Molecular Targeted Therapy, media_common, Pleural mesothelioma, business.industry, Platinum compounds, Mesothelioma, Malignant, Hematology, medicine.disease, Clinical trial, 030104 developmental biology, Pemetrexed, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Pleura, Molecular Profile, Human medicine, business, medicine.drug
Abstract

Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleura with a poor prognosis. The most active first-line regimens are platinum compounds and pemetrexed. There is no standard second-line treatment in MPM. Advances in the understanding of tumor molecular biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. Unfortunately none of the explored targeted treatments can currently be recommended as routine treatment in MPM. We reviewed the biological pathways involved in MPM, the clinical trials about targeted therapy, and possible related mechanisms of resistance. We suggest that specific genetic markers are needed as targets of selective therapy. By this way the selection of patients based on the molecular profile may facilitate a therapeutic strategy that allows the use of the most appropriate drug for each patient. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Published
2016

22. Treatment of Metastatic Colorectal Cancer Patients ≥75 Years Old in Clinical Practice: A Multicenter Analysis

Author

Luigi Di Lauro, Ida Pavese, Emanuela Risi, Marco Russano, Domenico Corsi, Carlo Signorelli, Diego Signorelli, Fabrizio Ciancola, Giada Cortese, Clara Natoli, Arianna Pellegrino, Federica Morano, Roberta Grande, Enzo Maria Ruggeri, Domenico Sergi, Isabella Sperduti, Germano Zampa, Teresa Gamucci, Carlo Garufi, Donatello Gemma, Grande, R., Natoli, C., Ciancola, F., Gemma, D., Pellegrino, A., Pavese, I., Garufi, C., Lauro, L. D., Corsi, D., Signorelli, D., Sperduti, I., Cortese, G., Risi, E., Morano, F., Sergi, D., Signorelli, C., Ruggeri, E. M., Zampa, G., Russano, M., and Gamucci, T.

Subjects
Oncology, Male, Colorectal cancer, Cancer Treatment, lcsh:Medicine, Kaplan-Meier Estimate, Gene mutation, medicine.disease_cause, Toxicology, Pathology and Laboratory Medicine, Gastroenterology, Metastasis, 0302 clinical medicine, Elderly, Basic Cancer Research, Medicine and Health Sciences, 030212 general & internal medicine, Neoplasm Metastasis, Practice Patterns, Physicians', lcsh:Science, Aged, 80 and over, Multidisciplinary, Pharmaceutics, Prognosis, Primary tumor, Surgical Oncology, 030220 oncology & carcinogenesis, Female, KRAS, Colorectal Neoplasms, Research Article, Clinical Oncology, medicine.medical_specialty, Surgical and Invasive Medical Procedures, 03 medical and health sciences, Drug Therapy, Median follow-up, Internal medicine, medicine, Chemotherapy, Humans, Propensity Score, Aged, Performance status, Toxicity, Proportional hazards model, business.industry, lcsh:R, Biology and Life Sciences, medicine.disease, Geriatrics, Age Groups, People and Places, lcsh:Q, Population Groupings, Clinical Medicine, business
Abstract

Background Colorectal cancer patients have a median age of incidence >65years although they are largely under-represented in phase-III trials. This large population contains patients unfit for treatment, those suitable for monotherapy or for doublets and the impact of chemotherapy outside clinical trial is unclear. The aim of the study was to retrospectively analyse Overall Survival(OS) of elderly metastatic colorectal cancer(mCRC) patients treated with chemotherapy in daily practice. Methods Kaplan-Meir method was used for OS, the log-rank or Tarone-Ware test for differences between subgroups, Cox’s proportional hazard model to assess the impact of known prognostic factors and treatment. Results 751 patients with mCRC observed between January 2000 and January 2013 were collected. Median age was 79 year(75–93); Male/Female 61/39%, ECOG-PS 0-1/2 85/15%; colon/rectum 74/26%; multiple metastatic sites 34%, only liver metastasis in 41% of patients. KRAS status was studied in 35% of patients: 44% of them showed gene mutation. 20.5% of patients did not received any kind of treatment including surgery. Comorbidities observed: cardiovascular 34%, diabetes 14%, hypertension 50%. Primary tumor was resected in 80.6%; surgery of liver metastasis was done in 19% of patients (2.3% of patients >80years). 78% of patients underwent chemotherapy. Median follow up was 12 months(range 1–124). Median OS was 17 months (CI 95%15–19);median OS in no-treated patients was 5 months (4–6); mOS of patients with at least one treatment was 20 months (18–22). In KRAS mutated group median OS was 19months (15–23) while in KRAS wild type patients median OS was 25 months (20–30). At multivariate analysis sex(Female), age(80 years old or with a poor performance status (respectively p

Published
2016

23. Beyond evidence-based data: Scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

Author

Clara Natoli, Viviana Bazan, Sergio Rizzo, Antonio Russo, Gianni Pantuso, Lorena Incorvaia, Giuseppe Badalamenti, Giuseppe Bronte, Incorvaia, L., Bronte, G., Bazan, V., Badalamenti, G., Rizzo, S., Pantuso, G., Natoli, C., and Russo, A

Subjects
0301 basic medicine, Oncology, medicine.medical_specialty, Evidence-based practice, medicine.drug_class, Settore MED/06 - Oncologia Medica, VEGF receptors, Antineoplastic Agents, Review, urologic and male genital diseases, renal cell cancer, Tyrosine-kinase inhibitor, 03 medical and health sciences, angiogenesis, 0302 clinical medicine, tyrosine kinase inhibitor, Quality of life, Renal cell carcinoma, Internal medicine, Angiogenesis, MTOR, Renal cell cancer, Tyrosine kinase inhibitor, VEGFr, medicine, Overall survival, Animals, Humans, Molecular Targeted Therapy, Precision Medicine, Carcinoma, Renal Cell, Therapeutic strategy, biology, business.industry, Precision medicine, medicine.disease, Kidney Neoplasms, Surgery, Angiogenesi, Settore MED/18 - Chirurgia Generale, 030104 developmental biology, 030220 oncology & carcinogenesis, biology.protein, mTOR, business
Abstract

The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition. Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.

Published
2016

24. PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

Author

Christian Rolfo, Angela Listì, Daniele Santini, Giuseppe Bronte, Giuseppe Cicero, Francesco Passiglia, Antonio Galvano, Clara Natoli, Sergio Rizzo, Antonio Russo, Viviana Bazan, Passiglia, F., Bronte, G., Bazan, V., Natoli, C., Rizzo, S., Galvano, A., Listì, A., Cicero, G., Rolfo, C., Santini, D., and Russo, A.

Subjects
0301 basic medicine, Oncology, PD-L1, medicine.medical_specialty, Lung Neoplasms, Anti-PD1/PD-L1 MoAbs, medicine.medical_treatment, Anti-PD1/PD-L1 MoAb, Antineoplastic Agents, Cochrane Library, NSCLC, B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Outcome Assessment, Health Care, Biomarkers, Tumor, Odds Ratio, Humans, Medicine, Lung cancer, Biology, biology, business.industry, Antibodies, Monoclonal, Immunotherapy, Odds ratio, Prognosis, medicine.disease, Predictive biomarker, Immunohistochemistry, Clinical trial, 030104 developmental biology, Clinical trials unit, Response Evaluation Criteria in Solid Tumors, 030220 oncology & carcinogenesis, Immunology, biology.protein, Human medicine, business, Research Paper
Abstract

// Francesco Passiglia 1, * , Giuseppe Bronte 1, * , Viviana Bazan 1, * , Clara Natoli 2 , Sergio Rizzo 1 , Antonio Galvano 1 , Angela Listi 1 , Giuseppe Cicero 1 , Christian Rolfo 3 , Daniele Santini 4 , Antonio Russo 1 1 Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy 3 Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium 4 Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy * These authors have contributed equally to this work Correspondence to: Antonio Russo, e-mail: antonio.russo@usa.net Keywords: PD-L1, predictive biomarker, immunotherapy, anti-PD1/PD-L1 MoAbs, NSCLC Received: December 03, 2015 Accepted: February 11, 2016 Published: February 22, 2016 ABSTRACT Background: Clinical trials of immune checkpoints modulators, including both programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, have recently shown promising activity and tolerable toxicity in pre-treated NSCLC patients. However the predictive role of PD-L1 expression is still controversial. This pooled analysis aims to clarify the association of clinical objective responses to anti PD-1/PD-L1 monoclonal antibodies (MoAbs) and tumor PD-L1 expression in pre-treated NSCLC patients. Methods: Data from published studies, that evaluated efficacy and safety of PD-1/PD-L1 inhibitors in pre-treated NSCLC patients, stratified by tumor PD-L1 expression status (immunohistochemistry, cut-off point 1%), were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer, meeting proceedings. Pooled Odds ratio (OR) and 95% confidence intervals (95% CIs) were calculated for the Overall Response Rate (ORR) (as evaluated by Response Evaluation Criteria in Solid Tumors, version 1.1), according to PD-L1 expression status. Results: A total of seven studies, with 914 patients, were eligible. Pooled analysis showed that patients with PD-L1 positive tumors (PD-L1 tumor cell staining ≥1%), had a significantly higher ORR, compared to patients with PD-L1 negative tumors (OR: 2.44; 95% CIs: 1.61-3.68). Conclusions: PD-L1 tumor over-expression seems to be associated with higher clinical activity of anti PD-1/PD-L1 MoAbs, in pre-treated NSCLC patients, suggesting a potential role of PD-L1 expression, IHC cut-off point 1%, as predictive biomarker for the selection of patients to treat with immune-checkpoint inhibitors.

Published
2016

25. The comparison of outcomes from tyrosine kinase inhibitor monotherapy in second- or third-line for advanced non-small-cell lung cancer patients with wild-type or unknown EGFR status

Author

Sergio Rizzo, Antonio Picone, Antonio Russo, Alessandro Russo, Vincenzo Adamo, Giuseppina Savio, Viviana Bazan, Livio Blasi, Tindara Franchina, Giovanni Sortino, Francesco Passiglia, Michele De Tursi, Agata Laudani, Giuseppe Bronte, Clara Natoli, Elisabetta Gambale, Massimiliano Alù, Claudia Celesia, Bronte, G., Franchina, T., Alù, M., Sortino, G., Celesia, C., Passiglia, F., Savio, G., Laudani, A., Russo, A., Picone, A., Rizzo, S., De Tursi, M., Gambale, E., Bazan, V., Natoli, C., Blasi, L., and Adamo, V.

Subjects
Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, medicine.drug_class, EGFR, Tyrosine kinase inhibitor, Kaplan-Meier Estimate, Tyrosine-kinase inhibitor, Erlotinib Hydrochloride, 03 medical and health sciences, 0302 clinical medicine, Gefitinib, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, Chemotherapy, Lung cancer, Protein Kinase Inhibitors, Chemotherapy, EGFR, Non-small-cell lung cancer, Tyrosine kinase inhibitor, Oncology, Aged, Retrospective Studies, Aged, 80 and over, Performance status, business.industry, Non-small-cell lung cancer, Retrospective cohort study, Middle Aged, medicine.disease, respiratory tract diseases, Surgery, ErbB Receptors, Clinical trial, Treatment Outcome, 030104 developmental biology, 030220 oncology & carcinogenesis, Mutation, Quinazolines, Female, Erlotinib, business, Research Paper, medicine.drug
Abstract

// Giuseppe Bronte 1, * , Tindara Franchina 2, * , Massimiliano Alu 3, * , Giovanni Sortino 1 , Claudia Celesia 1 , Francesco Passiglia 1 , Giuseppina Savio 3 , Agata Laudani 3 , Alessandro Russo 2 , Antonio Picone 2 , Sergio Rizzo 1 , Michele De Tursi 4 , Elisabetta Gambale 4 , Viviana Bazan 1 , Clara Natoli 4 , Livio Blasi 3 , Vincenzo Adamo 2 , Antonio Russo 1 1 Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy 3 Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy 4 Department of Medical, Oral and Biotechnological Sciences, University “G. D'Annunzio”, Chieti, Italy * These authors contributed equally to this work Correspondence to: Antonio Russo, email: antonio.russo@usa.net Keywords: non-small-cell lung cancer, EGFR, tyrosine kinase inhibitor, chemotherapy Received: January 21, 2016 Accepted: February 28, 2016 Published: March 16, 2016 ABSTRACT Background: Second-line treatment for advanced non-small-cell lung cancer (NSCLC) patients includes monotherapy with a third-generation cytotoxic drug (CT) or a tyrosine kinase inhibitor (TKI). These options are the actual standard for EGFR wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some clinical trials and meta-analyses investigated the comparison between CT and TKI in second-line, but data are conflicting. Methods: We designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records patients treated with at least 1 line of CT and at least 1 line of TKI. We collected data about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR status, treatment schedule, better response and time-to-progression (TTP) for each line of treatment and overall survival (OS). Results: 93 patients met selection criteria. Mean age 66,7 (range: 46–84). M/F ratio is 3:1. 39 EGFR-WT and 54 EGFR-UK. All patients received erlotinib or gefitinib as second-line treatment or erlotinib as third-line treatment. No TTP differences were observed for both second-line (HR:0,91; p = 0,6333) and third-line (HR:1.1; p = 0,6951) treatment (TKI vs CT). A trend of a benefit in OS in favor of 3rd-line TKI (HR:0,68; p = 0,11). Conclusions: This study explores the role of TKIs in EGFR non-mutated NSCLC patients. OS analysis highlights a trend to a benefit in patients who received TKI in third-line, even if this result is statistically non-significant. Further analysis are needed to find an explanation for this observation.

Published
2016

26. Unknown primary tumors

Author

Pier Giorgio Natali, Sergio Palmeri, Stefano Iacobelli, Nicola Tinari, Marco Salvatore, Matteo Landriscina, Clara Natoli, O. Nappi, M. Zilli, V. Ramazzotti, Patrizio Giacomini, Natoli,C, Ramazzotti,V, Nappi,O, Giacomini,P, Palmeri,S, Salvatore,M, Landriscina,M, Zilli,M, Natali,PG, Tinari,N, and Iacobelli,S

Subjects
Cancer Research, business.industry, Gene Expression Profiling, Biological entity, MEDLINE, Treatment options, Signs and symptoms, Bioinformatics, Functional imaging, MicroRNAs, Oncology, Unknown primary tumors, UPT, Immunology, Unknown Primary Tumors, Genetics, Unknown primary, Animals, Humans, Neoplasms, Unknown Primary, Medicine, business, Site of origin
Abstract

An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarray or miRNA classifications of UPTs have been used, with an accuracy in the prediction of the primary site as high as 90%. It should be noted that validating a prediction of tissue origin is challenging in these patients, since most of them will never have a primary site identified. Moreover, prospective studies to determine whether selection of treatment options based on such profiling methods actually improves patient outcome are still missing. In the last few years functional imaging (i.e. FDG-PET/CT) has gained a main role in the detection of the site of origin of UPTs and is currently recommended by the European Association of Nuclear Medicine. However, despite recent refinements in the diagnostic workup, the site of origin of UPT often remains elusive. As a consequence, treatment of patients with UPT is still empirical and inadequate.

Published
2011

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