Is progression-free survival a more relevant endpoint than overall survival in first-line HR+/HER2− metastatic breast cancer?
Authors Forsythe A, Chandiwana D, Barth J, Thabane M, Baeck J, Shor A, Tremblay G
Received 16 January 2018
Accepted for publication 8 March 2018
Published 4 May 2018 Volume 2018:10 Pages 1015—1025
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Professor Nakshatri
Anna Forsythe,1 David Chandiwana,2 Janina Barth,3 Marroon Thabane,4 Johan Baeck,5 Anastasiya Shor,1 Gabriel Tremblay6
1Health Technology Assessment Evidence, Purple Squirrel Economics, New York, NY, USA; 2Global Value and Access, Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 3German Market Access, Novartis Pharma GmbH, Nuremberg, Germany; 4Health Policy and Patient Access, Novartis Pharmaceuticals Incorporated, Dorval, QC, Canada; 5Global Medical Affairs (Oncology Business Unit), Novartis Pharmaceutical Corporation, East Hanover, NJ, USA; 6Health Economics, Purple Squirrel Economics, New York, NY, USA
Background: Hormone receptor-positive (HR+), human epidermal growth factor receptor 2- negative (HER2−), metastatic breast cancer (MBC) accounts for 73% of all MBCs. Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients with HR+/HER2− MBC. Novel therapies have demonstrated improvements in progression-free survival (PFS) compared to ET. The clinical relevance of PFS is being debated, as there is no proven direct correlation with overall survival (OS) benefit to date. We reviewed studies of HR+/HER2− MBC to assess PFS and other factors that influence OS and treatment response, and health-related quality of life (HRQoL).
Methods: The Embase®, Medline®, and Cochrane databases were systematically searched to identify studies in adult women with HR+/HER2− MBC, published between January 2006 and January 2017, and written in English. Phase II and III randomized controlled trials (RCTs), observational, and retrospective studies were included.
Results: Seventy-nine RCTs were identified: 58 (73%) in the 1L+ setting and 21 (27%) in second-line or greater settings. PFS hazard ratios (HRs) were reported in 61 (77%) studies; 31 (39%) reported significant PFS improvements. OS was reported in 44 (41%) studies; 12 (15%) reported significant OS improvements. Significant improvements in both PFS and OS were reported in only 6 (8%) studies (1 Phase II; 5 Phase III). Patients with HER2− MBC received, on average, ≥5 lines of therapy, with no consistent treatment pathway. Baseline characteristics, prior therapies, and the type and number of post-progression therapies significantly impacted OS. PFS, response rates, and HRQoL decreased with each line of therapy (EuroQol 5 Dimensions: 0.78 1L vs. 0.70 post-progression).
Conclusion: Few RCTs in HR+/HER2− MBC have demonstrated significant improvements in OS. Factors other than choice of 1L therapy impact OS, including post-progression therapies, which cannot be controlled in RCTs. This study emphasizes the importance of PFS improvement in 1L treatment of HR+/HER2− MBC.
Keywords: breast cancer, overall survival, progression-free survival, health-related quality of life, systematic literature review
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