The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer – a systematic review

Breast Cancer Research, Nov 2015

Introduction This study aimed at evaluating the overall survival (OS) gain associated with human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with metastatic breast cancer (mBC). Methods A bibliographic search was conducted in PubMed and Cochrane databases. Only phase III randomized controlled trials (RCTs) including HER2-positive (HER2+) mBC patients were included in this review. OS was defined as time from randomization until the occurrence of death from any cause. Studies have been grouped according to the line of treatment, i.e., first-line or second-line or beyond. Results Nineteen RCTs were eligible for inclusion, of which 12 assessed therapies targeting HER2+ mBC in the first-line setting. OS improved from 20.3 months in the first RCT (standard chemotherapy; Slamon et al. (N Engl J Med 344:783–92, 2001)) evaluating HER2-targeting therapies to 48 months in the study of Swain et al. (Lancet Oncol 14:461–71, 2013), with triple combination of pertuzumab, trastuzumab and docetaxel. Seven RCTs evaluated the OS of HER2-targeting therapies in the second-line setting and beyond. The OS in second-line setting improved from 15.3 months (capecitabine; Cameron et al. (Breast Cancer Res Treat 112:533–43, 2008)) to 30.7 months (trastuzumab emtansine; Verma et al. (N Engl J Med 367:1783–91, 2012)). In the third-line setting, the association of lapatinib and trastuzumab has demonstrated to improve OS to 4.5 months compared with lapatinib alone (14 months vs. 9.5 months; Blackwell et al. (J Clin Oncol 30:2585–92, 2012)). Conclusions HER2-directed therapies had an undeniable beneficial impact on the OS of patients with HER2+ mBC. The triple combination of docetaxel, pertuzumab and trastuzumab is associated with a survival extent of more than 4.5 years, compared with a life expectancy of 1.5 years achieved 14 years ago.

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The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer – a systematic review

Mendes et al. Breast Cancer Research The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer - a systematic review Diogo Mendes 0 1 3 Carlos Alves 0 1 3 Noémia Afonso 2 Fátima Cardoso 7 José Luís Passos-Coelho 6 Luís Costa 5 Sofia Andrade 4 Francisco Batel-Marques 0 1 3 0 Faculty of Pharmacy, University of Coimbra , Azinhaga de Santa Comba, 3000-548 Coimbra , Portugal 1 CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light and Image , Azinhaga de Santa Comba, Celas, 3000-548 Coimbra , Portugal 2 Medical Oncology Service, IPO - Portuguese Institute of Oncology Professor Francisco Gentil , Rua Dr. António Bernardino de Almeida, 4200-072 Oporto , Portugal 3 CHAD - Centre for Health Technology Assessment and Drug Research, AIBILI - Association for Innovation and Biomedical Research on Light and Image , Azinhaga de Santa Comba, Celas, 3000-548 Coimbra , Portugal 4 Market Access Department, Roche Pharmaceuticals , Estrada Nacional 249-1, 2720-413 Amadora , Portugal 5 Medical Oncology Service, Santa Maria Hospital , Rua de Santa Marta, 1169-024 Lisbon , Portugal 6 Medical Oncology Service, Hospital da Luz, Avenida Lusíada , 100, 1500-650 Lisbon , Portugal 7 Breast Cancer Unit, Champalimaud Cancer Center , Avenida De Brasília s/n, 1400-038 Lisbon , Portugal Introduction: This study aimed at evaluating the overall survival (OS) gain associated with human epidermal growth factor receptor 2 (HER2)-directed therapies in patients with metastatic breast cancer (mBC). Methods: A bibliographic search was conducted in PubMed and Cochrane databases. Only phase III randomized controlled trials (RCTs) including HER2-positive (HER2+) mBC patients were included in this review. OS was defined as time from randomization until the occurrence of death from any cause. Studies have been grouped according to the line of treatment, i.e., first-line or second-line or beyond. Results: Nineteen RCTs were eligible for inclusion, of which 12 assessed therapies targeting HER2+ mBC in the first-line setting. OS improved from 20.3 months in the first RCT (standard chemotherapy; Slamon et al. (N Engl J Med 344:783-92, 2001)) evaluating HER2-targeting therapies to 48 months in the study of Swain et al. (Lancet Oncol 14:461-71, 2013), with triple combination of pertuzumab, trastuzumab and docetaxel. Seven RCTs evaluated the OS of HER2-targeting therapies in the second-line setting and beyond. The OS in second-line setting improved from 15.3 months (capecitabine; Cameron et al. (Breast Cancer Res Treat 112:533-43, 2008)) to 30.7 months (trastuzumab emtansine; Verma et al. (N Engl J Med 367:1783-91, 2012)). In the third-line setting, the association of lapatinib and trastuzumab has demonstrated to improve OS to 4.5 months compared with lapatinib alone (14 months vs. 9.5 months; Blackwell et al. (J Clin Oncol 30:2585-92, 2012)). Conclusions: HER2-directed therapies had an undeniable beneficial impact on the OS of patients with HER2+ mBC. The triple combination of docetaxel, pertuzumab and trastuzumab is associated with a survival extent of more than 4.5 years, compared with a life expectancy of 1.5 years achieved 14 years ago. Introduction Breast cancer (BC) is the second most common cancer worldwide and, by far, the most frequent among women with an estimated 1.67 million new cases diagnosed in 2012 (25 % of all cancers) (Ferlay et al. [ 6 ]). BC is the fifth cause of death from cancer overall (522,000 deaths) and it is the most frequent cause of cancer death in women in less developed regions (324,000 deaths, 14.3 % of the total) (Ferlay et al. [ 6 ]). In the developed countries, it is the second cause of cancer death (198,000 deaths, 15.4 %), after lung cancer (Ferlay et al. [ 6 ]). In developed countries between 6 and 10 % of women will have metastatic disease when diagnosed with BC (Dawood et al. [ 7 ]); in developing countries this percentage can reach 60 %. Depending on initial stage, tumor biology, and type of treatment scheme received, between 30 and 50 % of women with early BC will relapse (Cardoso et al. [ 8 ]). The amplification of the human epidermal growth factor receptor 2 (HER2) is observed in 25 to 30 % of all BCs (Slamon et al. [ 1 ]). Patients with BC with overexpression of HER2 have, originally, a poorer prognosis and shorter overall survival (OS) (Tandon et al. [ 9 ]; Slamon et al. [ 10 ]). The development of effective HER2-targeted drugs is considered a major breakthrough in BC therapy. Trastuzumab was the first anti-HER2 drug approved for treatment of HER2-positive (HER2+) metastatic BC, either alone or in combination with chemotherapy (Slamon et al. [ 1 ]). This anti-HER2 monoclonal antibody was associated with a significantly longer time to disease progression, higher response rate, longer response duration, and improved overall survival (Slamon et al. [ 1 ] (...truncated)


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Diogo Mendes, Carlos Alves, Noémia Afonso, Fátima Cardoso, José Passos-Coelho, Luís Costa, Sofia Andrade, Francisco Batel-Marques. The benefit of HER2-targeted therapies on overall survival of patients with metastatic HER2-positive breast cancer – a systematic review, Breast Cancer Research, 2015, pp. 140, 17, DOI: 10.1186/s13058-015-0648-2