New agents (nas) in metastatic castration-resistant prostate cancer (mcrpc): is there a sequence better than the others?

Abstract

Background: The availability of NAs (abiraterone, cabazitaxel and enzalutamide) for the treatment of mCRPC patients who progress after docetaxel and the possibility of using them sequentially has significantly improved clinical outcomes in advanced disease. However, the lack of head to head clinical trials as well as recent evidences of a possible cross-resistance among NAs have opened a debate about the best treatment sequence when these drugs are used the one after the other. We performed a systematic review and analysis of the retrospective studies assessing the outcomes of mCRPC patients treated with one third-line NA after having previously received docetaxel and another NA, in order to assess if a sequence strategy was better than the others. Methods: We analyzed all studies reporting monthly OS rates of mCRPC patients receiving two NAs after docetaxel published or reported until March 2015. The treatments were merged into three groups: one HNA followed by another, one NHA followed by CABA, and CABA followed by one HNA. The cumulative monthly OS rates in each group were determined using a weighted-average approach. To exclude potential selection biases, known prognostic factors (age, performance status, sites of metastases and Gleason score) were also evaluated. Results: 13 retrospective studies including 1022 patients who received one specific third-line NA after another NA administered as second-line: 1) 481 patients (HNA? HNA); 2) 312 patients (HNA?CABA); 3) 229 patients (CABA?HNA), were analyzed. No statistically significant differences in terms of baseline known prognostic factors have been observed. The 12-months OS rates were 28.5%, 61.3% and 76.4%, respectively. Conclusions: With all limits of retrospective nature, limited cohort size and potential selection biases of included studies, the present report did not demonstrate a clear superiority of a single drug over the others in the third-line setting of mCRPC. A possible OS advantage seems to be observed in the treatment sequences with CABA. However, prospective larger studies are required to validate these results, hoping head to head comparison trials. Our analysis confirms a potential cumulative survival benefit of sequential use of NAs in mCRPC.