Adding enzalutamide, rather than a conventional nonsteroidal antiandrogen (NSAA), to testosterone suppression offers a clinically meaningful improvement in overall survival for patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to updated findings from the ENZAMET trial presented at the 2002 ASCO Annual Meeting.

The latest analysis “extends and confirms the finding that enzalutamide added to testosterone suppression and compared to an active comparator provides a clinically meaningful improvement in overall survival for the combined study cohort with metastatic hormone-sensitive prostate cancer,” said principal investigator Ian D. Davis, MBBS, PhD, of Monash University and Eastern Health in Victoria, Australia.

“Benefits were most apparent for those with low-volume disease and especially for those for whom early docetaxel was not deemed necessary,” he added. “Enzalutamide should be considered in all patients with metastatic disease and especially in those for whom docetaxel is considered unsuitable or unlikely to be beneficial.”

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For this trial ( Identifier: NCT02446405), investigators randomly assigned 1125 patients with a median age of 69 years to receive testosterone suppression plus either enzalutamide or a conventional NSAA, with or without docetaxel. The researchers stratified patients by volume of metastasis (high vs low) and planned early docetaxel (yes vs no) as well as other subgroups. Of the 1125 patients, 602 had high-volume metastatic disease and 503 had planned early use of docetaxel.

The first planned interim analysis of ENZAMET, with 243 deaths after a median follow-up of 34 months, revealed a clinically meaningful 33% decreased risk of death in patients with mHSPC with the addition of enzalutamide to standard of care. The updated findings are from a prespecified analysis triggered to occur after 470 deaths. 

The latest analysis confirms the survival benefit of enzalutamide in mHSPC, at a median 68 months of follow-up. Based on 476 deaths and a cutoff date of January 19, 2022, patients who received enzalutamide had a significant 30% decreased risk of death compared with those receiving a conventional NSAA (95% CI, 0.58-0.84; P <.0001), Dr Davis reported. The median overall survival was 73.2 months in the NSAA group and not reached in the enzalutamide group.

The survival benefit of enzalutamide was more pronounced in patients with low-volume disease but also observed in patients with high-volume mHSPC, despite their relatively high survival with testosterone suppression plus docetaxel plus NSAA, according to Dr Davis. Exploratory analyses show that enzalutamide is active in all prognostic subgroups, including those in which docetaxel seems least active, he said.

“Triple therapy with testosterone suppression, docetaxel, and enzalutamide is, of course, only relevant for those able and willing to be treated with early docetaxel,” Dr Davis said. “Exploratory analyses raise the hypothesis that the greatest benefits of this triplet therapy … might be limited to those with the poorest prognosis disease, particularly synchronous and high-volume metastatic disease.”


Martin AJ, Zielinski RR, Thomson A, et al. Updated overall survival outcomes in ENZAMET (ANZUP 1304), an international, cooperative group trial of enzalutamide in metastatic hormone-sensitive prostate cancer (mHSPC). Presented at ASCO 2022; June 3-8, 2022. Abstract LBA5004.