Overall survival (OS) endpoint: an incomplete evaluation of metastatic breast cancer (MBC) treatment outcome

Overall survival (OS) has been debated as the most important clinical endpoint in metastatic breast cancer (MBC) trials mainly because survival could be influenced by treatment after progression in an era of effective subsequent-line agents. We conducted a search strategy using PubMed for all the phase 3 trials in the last two decades evaluating survival outcome in MBC. We investigated the frequency of trials reporting survival outcome and response/resistance to treatment beyond progression. One hundred fifteen trials met our eligibility criteria: 69 (60 %) evaluated chemotherapy regimens (group A), 32 (28 %) evaluated targeted therapies (group B), and 14 (12 %) focused on endocrine treatment (group C). An OS benefit was demonstrated in approximately 22 % of the trials in each group. Less than 10 % of the trials in group A and B reported response data after progression on trial therapy. Post-progression treatment resistance was only reported in group A in 3 % (2/69) of the trials. In addition, the number of lines of treatment used post-progression was reported in 14 % (10/69), 9.4 % (3/32), and 14 % (2/14) of the trials in group A, B, and C, respectively. Post-progression survival and its effect on OS was reported in only 1 % (1/69), 3 % (1/32), and 7 % (1/14) of the trials for group A, B, and C respectively. A clear paucity of post-progression treatment information is noted in the majority of the phase 3 trials for MBC. We do know that OS can be affected partially or directly by treatments used after progression. In order to assess the true clinical benefit of a new drug and to have a complete evaluation of OS outcome, a detailed collection of post-progression treatment information is required and should be mandated in MBC trials.