Enzalutamide performs well in metastatic hormone-sensitive prostate cancer

Enzalutamide added to testosterone suppression outperformed testosterone suppression plus standard nonsteroidal anti-androgen (NSAA) therapy in patients with metastatic hormone-sensitive prostate cancer (mHSPC) in the ENZAMET trial. The benefits in overall survival (OS) were most pronounced in patients with low-volume disease who did not receive early or concurrent docetaxel.

The phase 3 ENZAMET trial (NCT02446405) randomised 1,125 patients with mHSPC to testosterone suppression plus standard NSAA therapy (control arm) or testosterone suppression plus enzalutamide (experimental arm). The administration of prior or concurrent docetaxel was allowed at investigator’s discretion. The first interim analysis of this trial, performed in 2019, displayed an OS benefit for patients in the enzalutamide arm, but not if these patients were planned to receive early docetaxel [1]. At ASCO 2022, Prof. Ian Davis (Monash University, Australia) presented the second interim analysis of this trial [2].

After a median follow-up of 68 months, the OS benefit of patients in the enzalutamide arm was maintained (median OS 73.2 months vs ‘not reached’; HR 0.70; P<0.0001, see Figure). In addition, the corresponding 5-year OS rates were 67% and 57%. Prof. Davis added that 76% of the patients in the control arm received enzalutamide or abiraterone after progression compared with 26% of the patients in the experimental arm. Prespecified subgroup analyses suggested that the OS benefits of enzalutamide were apparent across subgroups, but that patients with low-volume disease who were not planned for early docetaxel (55%) may benefit the most from enzalutamide. Importantly, a clear benefit of enzalutamide on top of testosterone suppression and docetaxel was observed in patients with synchronous de novo disease (n=362; HR 0.73; 95% CI 0.55–0.99). The study was however not powered for the subgroup analyses so these results should be interpreted with caution.

Figure: Overall survival outcomes of ENZAMET [2]



“Although enzalutamide was already used widely in patients with mHSPC, largely because of the results of the ENZAMET study, the current analysis provides more rationale for the use of enzalutamide after docetaxel or with concurrent docetaxel,” argued Prof. Russel Szmulewitz (University of Chicago, IL, USA), discussant of this presentation.

1. Davis ID, et al. N Engl J Med. 2019;381(2):121–131.
2. Davis ID, et al. Updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). LBA5004, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August, 202218 March, 2024