Beyond convention in treatment of metastatic breast cancer—rediscover overall survival

The Holy Grail of palliative chemotherapy in metastatic breast cancer should always be a meaningful extension of overall survival (OS). While an improvement in OS remains a sine qua non in clinical trials for many tumour groups, progression-free survival (PFS) has replaced OS as the primary end-point in most clinical trials for metastatic breast cancer. The reasons for forgoing OS in metastatic breast cancer trials are many. Chief amongst these would be the confounding effect of additional lines of treatment post progression following the study drug abrogating any inherent improvement in OS. PFS has been looked upon as a more sensitive endpoint than OS in detecting the potential benefit of a new treatment. An adequately powered trial based on PFS as the primary end-point requires a smaller patient number and a shorter follow-up period. Interestingly, the approval of the new anti-tubulin molecule eribulin in 2012 for use in pre-treated metastatic breast cancer was based on improvement in OS. This was followed by the approval of pertuzumab and T-DM1, though based on improvement in PFS, both demonstrated significant improvement in OS. These recent developments showed that OS remains a reachable end-point in many scenarios.