355PD - Overall survival (OS) endpoint: An incomplete evaluation of metastatic breast cancer (MBC) treatment outcome

Date 28 September 2014
Event ESMO 2014
Session Metastatic and locally advanced breast cancer: Facing with heterogeneity and endpoints in clinical trials
Topics Breast Cancer, Metastatic
Presenter Jacques Raphael
Citation Annals of Oncology (2014) 25 (suppl_4): iv116-iv136. 10.1093/annonc/mdu329
Authors J. Raphael1, S. Verma2
  • 1Dept. Medical Oncology, Sunnybrook Odette Cancer Center, Sunnybrook HSC, M4N 3M5 - Toronto/CA
  • 2Medical Oncology, Sunnybrook Odette Cancer Center, Sunnybrook HSC, M4N 3M5 - Toronto/CA

Abstract

Aim

Background: OS has been historically considered the most important therapeutic objective in MBC; however survival could be influenced by treatment after progression in an era of effective subsequent-line agents.

Methods

We conducted a search strategy using PubMed for randomized phase 3 trials published in the last 2 decades (1994-2014) evaluating survival outcome in MBC. We investigated the frequency of trials reporting survival outcomes post progression and responses/resistance to subsequent treatments in the recent literature.

Results

110 trials met our eligibility criteria: 69 (63%) compared chemotherapy regimens (group A), 27 (25%) compared targeted therapy (Group B) and 14 (13%) evaluated endocrine treatment alone (Group C). In Group A, 59% of the trials evaluated treatment in the 1st line setting, 7% had OS as a primary endpoint. In Group B, 70% of the trials were in the 1st line setting, 11% had OS as a primary endpoint. In Group C, 57% of the trials were in the 1st line setting and 7% evaluated OS as a primary endpoint. For group A, an OS benefit was reached in 4% and 17% of the trials when used as a primary and secondary endpoint respectively. The benefit was demonstrated in 11% and 11% of the trials respectively for group B and 0% and 21% of the trials respectively for group C. Post progression survival (PPS) was reported in only 1%, 4% and 7% of the trials for group A, B and C respectively. Details of treatments after progression are described in table 1.  

Post progression treatment characteristics

Phase 3 trials by group N = 110 (%) N* reporting Tx** category after P*** (overall/by group (%)) N reporting response data for Tx after P (overall/by group (%)) N reporting response duration (overall/by group (%)) N reporting Tx resistance information (overall/by group (%)) N reporting number of lines of Tx used after P (overall/by group (%)) N reporting specific Tx information after P (overall/by group (%))
Group A= 69 (63%) 28 (25%/41%) 7 (6%/10%) 6 (5%/9%) 2 (2%/3%) 10 (9%/14%) 27 (25%/39%)
Group B= 27 (25%) 8 (7%/30%) 1 (1%/4%) 1 (1%/4%) 0 3 (3%/11%) 8 (7%/30%)
Group C= 14 (13%) 5 (5%/36%) 4 (4%/29%) 3 (3%/21%) 0 2 (2%/14%) 5 (5%/36%)

* Number of trials, ** Treatment.

Conclusions

Conclusion: OS benefit was significant in approximately quarter of the trials. Less than 10% of trials report PPS and treatment responses after progression. In order to assess the true clinical benefit of a new drug, a complete evaluation of survival outcome and subsequent treatments is needed in such trials with better guidelines for study design.

Disclosure

S. Verma: Advisory Board – Roche, EISAI, Amgen, Novartis, Astra Zeneca. All other authors have declared no conflicts of interest.