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 & 28 others 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, Teresa Gamucci

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)56921-56931
Number of pages11
JournalOncotarget
Volume8
Issue number34
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Observational Studies
Breast Neoplasms
Survival
ado-trastuzumab emtansine
pertuzumab
Disease-Free Survival
Multivariate Analysis
Retrospective Studies
Neoplasm Metastasis
Brain
Therapeutics
Neoplasms

Keywords

  • HER2 positive
  • Metastatic breast cancer
  • Previous pertuzumab
  • Real-world
  • T-DM1

ASJC Scopus subject areas

  • Oncology

Cite this

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

In: Oncotarget, Vol. 8, No. 34, 01.01.2017, p. 56921-56931.

Research output: Contribution to journalArticle

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, AF, Zampa, G, Mauri, M, D'Onofrio, L, Sini, V, Barba, M, Maugeri-Saccà, M, Rossi, E, Landucci, E, Tomao, S, Alberti, AM, 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 & Gamucci, T 2017, 'A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: A real-world experience', Oncotarget, vol. 8, no. 34, pp. 56921-56931. https://doi.org/10.18632/oncotarget.18176
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-Saccà, 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. / A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer : A real-world experience. In: Oncotarget. 2017 ; Vol. 8, No. 34. pp. 56921-56931.
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T1 - A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer

T2 - A real-world experience

AU - Vici, Patrizia

AU - Pizzuti, Laura

AU - Michelotti, Andrea

AU - Sperduti, Isabella

AU - Natoli, Clara

AU - Mentuccia, Lucia

AU - Di Lauro, Luigi

AU - Sergi, Domenico

AU - Marchetti, Paolo

AU - Santini, Daniele

AU - Magnolfi, Emanuela

AU - Iezzi, Laura

AU - Moscetti, Luca

AU - Fabbri, Agnese

AU - Cassano, Alessandra

AU - Grassadonia, Antonino

AU - Omarini, Claudia

AU - Piacentini, Federico

AU - Botticelli, Andrea

AU - Bertolini, Ilaria

AU - Scinto, Angelo Fedele

AU - Zampa, Germano

AU - Mauri, Maria

AU - D'Onofrio, Loretta

AU - Sini, Valentina

AU - Barba, Maddalena

AU - Maugeri-Saccà, Marcello

AU - Rossi, Ernesto

AU - Landucci, Elisabetta

AU - Tomao, Silverio

AU - Alberti, Antonio Maria

AU - Giotta, Francesco

AU - Ficorella, Corrado

AU - Adamo, Vincenzo

AU - Russo, Antonio

AU - Lorusso, Vito

AU - Cannita, Katia

AU - Barni, Sandro

AU - Laudadio, Lucio

AU - Greco, Filippo

AU - Garrone, Ornella

AU - Della Giulia, Marina

AU - Marolla, Paolo

AU - Sanguineti, Giuseppe

AU - Di Cocco, Barbara

AU - Ciliberto, Gennaro

AU - De Maria, Ruggero

AU - Gamucci, Teresa

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AB - 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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KW - Metastatic breast cancer

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