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, Metastatic
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.