ASCO GUCS 2016. Abstract 308. Optimal sequencing of enzalutamide and abiraterone in men with metastatic castration-resistant prostate cancer (mCRPC).

Benjamin Louis Maughan et al.

Results: 71 patients were identified: 58 received abi-to-enza and 13 received enza-to-abi. Comparisons of baseline characteristics between groups identified differences in PSA levels (P = 0.007), hemoglobin (P < 0.001), and presence of visceral disease (P = 0.035). The abi-to-enza group had a longer combined PFS than the enza-to-abi group: median 16.3 vs 12.5 mo (HR 0.53, P = 0.04). There was also a numeric improvement in OS in the abi-to-enza group compared to the enza-to-abi group: median 29.0 vs 21.0 mo (HR 0.51, P < 0.10). In multivariable analyses incorporating PSA level, hemoglobin, visceral disease and prior docetaxel use, both combined PFS (HR 2.59, P = 0.03) and OS (HR 4.59, P < 0.01) demonstrated improved outcomes with the abi-to-enza sequence.

Conclusions: This hypothesis-generating study potentially suggests superior PFS and OS in men with mCRPC receiving abiraterone then enzalutamide (compared to enzalutamide then abiraterone), although this could be due to baseline imbalances or the small sample size of this study. Prospective validation of this concept is ongoing (NCT02125357).

CARE™ Faculty Perspective: Challenges have arisen with regards to treatment selection and sequencing, due to the availability of more agents. In keeping with other similarly small and retrospective series, this study sheds a little more light on sequencing of enzalutamide and abiraterone, and suggests that there is potentially a better PFS and OS for patients receiving abiraterone followed by enzalutamide, vs. enzalutamide followed by abiraterone.  Despite these data, optimal sequencing of these agents is still not properly determined and more data are needed and anticipated.