Eight-year outcomes of testosterone suppression plus enzalutamide or a non-steroidal anti-androgen for metastatic hormone-sensitive prostate cancer

The multinational phase 3 ENZAMET study compared addition of enzalutamide versus a first-generation non-steroidal anti-androgen (NSAA) to testosterone suppression for metastatic hormone-sensitive prostate cancer (mHSPC). At median follow-ups of 34 and 68 months, the overall survival was better in the enzalutamide group. Eight-year results of the study have now been published. At a median follow-up of 97 months, deaths occurred in 258 of 563 (51%) of participants in the enzalutamide group versus 337 of 562 (60%) of participants in the NSAA group. Median overall survival was 7.9 versus 5.8 years, with OS at 8 years 50% versus 40% (HR 0.73; p=0.0001), with clinical progression-free survival at 8 years 43% versus 20% (HR 0.49; p<0.0001). Of 622 deaths, 468 were attributed to prostate cancer and were fewer with enzalutamide than with NSAA (207 versus 261), whereas deaths attributed to other causes occurred with similar frequency in the two groups )78 versus 76). Median treatment duration was 4.8 years in the enzalutamide group and 1.9 years in the NSAA group. Rate of grade 3-5 adverse events per 100 person-years were similar between groups for cardiac (2.2 versus 2.2) and nervous system (2.3 versus 2.0) disorders, with more falls observed with enzalutamide (0.70 versus 0.24). The authors conclude that enzalutamide plus testosterone suppression continues to provide substantial long-term overall survival benefit compared with NSAA plus testosterone suppression, with sustained efficacy an no increase in non-prostate cancer mortality.