Relationship between time to treatment failure and survival and between time to response and response duration in metastatic breast cancer. Implications for treatment.

The hypothesis that longer times to response (TTR) and times to treatment failure (TTF) are associated with a more chronic disease resulting in progressively longer response durations (TRTF) and times from treatment failure to death (TFTD) was evaluated in metastatic breast carcinoma. Data from 553 patients across two similar Eastern Cooperative Group combination chemotherapy trials was utilized to evaluate the relationship between TTR and TRTF, and TTF and TFTD. The TTR did not appear to predict for TRTF, which was approximately 7.6 months irrespective of TTR durations from 1 to 6+ months. The TFTD increased to approximately 8 months as the TTF increased to 6 months; thereafter, the TFTD remained stable up to at least 17 months of TTF. The discordance in the results of the two analyses suggests that the operational hypothesis is not necessarily true. However, these data, along with the subset analyses and previous animal and human studies, were taken as evidence that ultimate survival is selected by the response to the first regimen employed, that the primary therapeutic impact of a regimen is in the first 3-6 months, and that the regimen should maximize therapy early to achieve rapid complete remissions.