261P - Is PFS a more relevant endpoint than OS in 1L HR+, HER2– MBC? A systematic literature review

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Breast Cancer
Presenter Anna Forsythe
Citation Annals of Oncology (2017) 28 (suppl_5): v74-v108. 10.1093/annonc/mdx365
Authors A. Forsythe1, D. Chandiwana2, J. Barth3, M. Thabane4, J. Baeck2, A. Shor1, G. Tremblay1
  • 1Purple Squirrel Economics, Purple Squirrel Economics, 10010 - New York/US
  • 2Oncology, Novartis Pharmaceuticals Corporation, 07936-1080 - East Hanover/US
  • 3Oncology, Novartis Pharma GmbH, Nuremberg/DE
  • 4Oncology, Novartis Pharmaceuticals Canada Inc., Dorval/CA



Hormone receptor-positive (HR+), human epidermal growth factor 2 receptor-negative (HER2–) metastatic breast cancer (MBC) accounts for 73% of all MBC.1 Endocrine therapy (ET) is the basis of first-line (1L) therapy for patients (pts) with HR+, HER2– MBC; however, efficacy is limited by ET resistance. Novel therapies have demonstrated improvements in progression-free survival (PFS) vs standard ET. The clinical relevance of PFS is debated due to a lack of direct correlation with overall survival (OS) benefit, and cases of asymptomatic progression. We review studies of HR+ HER2– MBC to assess factors that influence OS and treatment response, and changes in health-related quality of life (HRQoL).


The Embase®, MEDLINE®, and Cochrane databases were systematically searched to identify studies in adult women with HR+, HER2– MBC, published 2006–January 2017, and written in English. Phase (Ph) 2 and 3 randomized controlled-trials (RCTs), observational, and retrospective studies were considered and HRQoL and real-world evidence reviewed.


79 RCTs were identified: 58 (73%) in the 1L setting and 21 (27%) in the ≥second-line setting. PFS data were reported in 61 (77%) studies; 31 (51%) reported significant PFS improvement. OS was reported in 44 (56%) of studies; only 11 (14%) reported a significant OS improvement. Significant improvements in both PFS and OS were reported in only 6 (8%) studies (1 Ph 2; 5 Ph 3). Pts with HER2– MBC received on average ≥5 lines of therapy, with no defined 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 (EQ-5D: 0.78 1L vs 0.70 post-progression).


Multiple HR+, HER2– MBC therapies have been investigated yet few CTs have achieved a significant improvement in OS. Multiple factors besides the choice of 1L therapy impact OS, such as post-progression therapies, which cannot be controlled in RCTs. This study emphasizes the importance of PFS improvement coupled with HRQoL maintenance in 1L treatment of HR+, HER2– MBC. 1. Howlader N et al. J Natl Cancer Inst 2014;106:dju055.

Clinical trial identification

Legal entity responsible for the study

Novartis Pharmaceuticals Corporation


Novartis Pharmaceuticals Corporation


A. Forsythe: Consultant for Novartis. D. Chandiwana, M. Thabane, J. Baeck: Novartis employee and Novartis stocks/shares. J. Barth: Novartis employee. All other authors have declared no conflicts of interest.