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

Patrizia Vici _, Laura Pizzuti, Andrea Michelotti, Isabella Sperduti, Clara Natoli, Lucia Mentuccia, Luigi Di Lauro, Domenico Sergi, Paolo Marchetti, Daniele Santini, Emanuela Magnolfi, Laura Iezzi, Luca Moscetti, Agnese Fabbri, Alessandra Cassano, Antonino Grassadonia, Claudia Omarini, Federico Piacentini, Andrea Botticelli, Ilaria Bertolini, Angelo Fedele Scinto, Germano Zampa, Maria Mauri, Loretta D’Onofrio, Valentina Sini, Maddalena Barba, Marcello Maugeri-Saccà, Ernesto Rossi, Elisabetta Landucci, Silverio Tomao, Antonio Maria Alberti, Francesco Giotta, Corrado Ficorella, Vincenzo Adamo, Antonio Russo, Vito Lorusso, Katia Cannita, Sandro Barni, Lucio Laudadio, Filippo Greco, Ornella Garrone, Marina Della Giulia, Paolo Marolla, Giuseppe Sanguineti, Barbara Di Cocco, Gennaro Ciliberto, Ruggero De Maria and Teresa Gamucci

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Oncotarget. 2017; 8:56921-56931. https://doi.org/10.18632/oncotarget.18176

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Abstract

Patrizia Vici1, Laura Pizzuti1, Andrea Michelotti2, Isabella Sperduti3, Clara Natoli4, Lucia Mentuccia5, Luigi Di Lauro1, Domenico Sergi1, Paolo Marchetti6, Daniele Santini7, Emanuela Magnolfi5, Laura Iezzi4, Luca Moscetti8, Agnese Fabbri9, Alessandra Cassano10, Antonino Grassadonia4, Claudia Omarini11, Federico Piacentini11, Andrea Botticelli6, Ilaria Bertolini2, Angelo Fedele Scinto12, Germano Zampa13, Maria Mauri14, Loretta D’Onofrio7, Valentina Sini6, Maddalena Barba1, Marcello Maugeri-Saccà1, Ernesto Rossi10, Elisabetta Landucci2, Silverio Tomao15, Antonio Maria Alberti16, Francesco Giotta17, Corrado Ficorella18, Vincenzo Adamo19, Antonio Russo20, Vito Lorusso17, Katia Cannita18, Sandro Barni21, Lucio Laudadio22, Filippo Greco23, Ornella Garrone24, Marina Della Giulia1, Paolo Marolla1, Giuseppe Sanguineti25, Barbara Di Cocco26, Gennaro Ciliberto27, Ruggero De Maria28 and Teresa Gamucci5

1Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, Rome, Italy

2UO Oncologia Medica I, Ospedale S. Chiara, Dipartimento di oncologia, dei trapianti e delle nuove tecnologie, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

3Bio-Statistics Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy

4Department of Medical, Oral and Biotechnological Sciences, Centro Scienze dell’Invecchiamento e Medicina Traslazionale (CeSI-MeT), Chieti, Italy

5Medical Oncology Unit, ASL Frosinone, Frosinone, Italy

6Medical Oncology Unit, Policlinico Sant'Andrea, Rome, Italy

7Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy

8Division of Medical Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy

9Division of Oncology, Complesso Ospedaliero Belcolle, AUSL Viterbo, Viterbo, Italy

10Department of Medical Oncology, Catholic University of Sacred Heart, Rome, Italy

11Division of Medical Oncology, Department of Medical and Surgical Sciences for Children & Adults, University Hospital of Modena, Modena, Italy

12Medical Oncology, Ospedale San Giovanni Calibita Fatebenefratelli, Rome, Italy

13Oncology Unit, Nuovo Regina Margherita Hospital, Rome, Italy

14Division of Oncology, San Giovanni Hospital, Rome, Italy

15Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, Italy

16Medical Oncology, Sandro Pertini Hospital, Rome, Italy

17Division of Medical Oncology, IRCCS, Giovanni Paolo II Hospital, Bari, Italy

18Medical Oncology, Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L’Aquila, Italy

19Medical Oncology Unit AOOR Papardo-Piemonte, Department of Human Pathology of Adult And Evolutive Age “Gaetano Barresi”, University of Messina, Messina, Italy

20Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy

21Medical Oncology, ASST Bergamo Ovest, Ospedale di Treviglio, Bergamo, Italy

22Medical Oncology, Ospedale F. Renzetti, Lanciano, Italy

23Department of Pathology, Surgery and Oncology, “Mater Salutis” Hospital, ULSS21, Verona, Italy

24Medical Oncology, A.O. Ospedale di Insegnamento S. Croce e Carle, Cuneo, Italy

25Department of Radiotherapy, IRCCS Regina Elena National Cancer Institute, Rome, Italy

26Medical Oncology, S.M. Goretti Hospital, Latina, Italy

27Scientific Direction, IRCCS Regina Elena National Cancer Institute, Rome, Italy

28Institute of General Pathology, Catholic University of the Sacred Heart, Rome, Italy

Correspondence to:

Patrizia Vici, email: [email protected]

Keywords: metastatic breast cancer, HER2 positive, T-DM1, previous pertuzumab, real-world

Received: March 07, 2017     Accepted: April 21, 2017     Published: May 25, 2017

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.


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