medwireNews: Men with metastatic castration-sensitive prostate cancer (CSPC) derive a significant overall survival (OS) benefit from the addition of enzalutamide to standard testosterone suppression, show phase III trial results.
A “clear benefit” was seen regardless of disease volume and among individuals who did not use concurrent docetaxel, but the findings were less robust for the subgroup that received concomitant docetaxel, reported Christopher Sweeney (Dana-Farber Cancer Institute, Boston, Massachusetts, USA) at the 2019 ASCO Annual Meeting, held in Chicago, Illinois, USA.
The ENZAMET (Enzalutamide in First Line Androgen Deprivation Therapy for Metastatic Prostate Cancer) trial enrolled 1125 men with metastatic hormone-sensitive disease and randomly assigned them to receive either enzalutamide 160 mg/day or a standard nonsteroidal anti-androgen (NSAA; bicalutamide, nilutamide, or flutamide) alongside androgen deprivation therapy.
Unlike the ARCHES trial of enzalutamide and the TITAN trial of apalutamide, both also in the metastatic CSPC setting, ENZAMET allowed the use of concurrent docetaxel, with the decision to use it or not left up to individual patients and their physicians, Sweeney explained.
At the time of analysis, patients had been followed up for a median of 34 months, and the risk for death was a significant 33% lower for the enzalutamide than control group. The median was unreached for both treatment arms, but the estimated rates for OS at 3 years were 80% and 72%, respectively.
The risk for prostate-specific antigen (PSA) and clinical progression was also significantly reduced for men given enzalutamide versus a standard NSAA, by 61% and 60%, respectively, and the corresponding rates for PSA and clinical progression-free survival (PFS) at 3 years were 67% versus 37% and 68% versus 41%.
Subgroup analysis showed that men with a high or low volume of disease derived a survival benefit from the addition of enzalutamide rather than a standard NSAA to testosterone suppression, with estimated 3-year OS rates of 71% versus 64% and 90% versus 82%, respectively, as did the subgroup of men who did not use concomitant docetaxel, at 83% versus 70%.
However, the 3-year OS rates were comparable for enzalutamide and standard NSAA treatment among individuals with concurrent docetaxel use, at 74% and 75%, respectively.
By contrast, all subgroups had significantly better clinical PFS with enzalutamide than a standard NSAA.
With regard to safety, a higher proportion of men in the enzalutamide than control groups reported adverse events (AEs) of grade 3–5 (57 vs 43%) and serious AEs (42 vs 34%), but Sweeney explained that when the duration of treatment exposure was taken into account, the serious AEs rates were comparable between groups (0.33 vs 0.34 AEs per year of exposure).
Clinically significant fatigue (grade 2) occurred in 25% of participants receiving enzalutamide and 14% of those given a standard NSAA, and there were seven cases of seizure in the enzalutamide group compared with none in the control group.
The incidence of certain AEs was higher among patients who did versus did not receive concurrent docetaxel; for instance, grade 2 peripheral neuropathy occurred in 9% and 3% of enzalutamide- and standard NSAA-treated participants who received docetaxel, with corresponding rates of 0% and less than 1% for those who did not.
In light of these results, Sweeney concluded: “For patients who are candidates for docetaxel when starting testosterone suppression, quality of life analyses and longer follow-up are needed to determine whether the delay in progression with concurrent enzalutamide, results in a meaningful clinical benefit and/or is compounded by [castration-resistant prostate cancer] therapy and augments survival beyond 3 years.”
Asked about how physicians would choose between enzalutamide, apalutamide, abiraterone, and chemotherapy, Sweeney told medwireNews that “all options have to be on the table,” and that physicians and patients have to discuss and make their choices based on “financial concerns, comorbidities, and preferences.”
ASCO expert Neeraj Agarwal (University of Utah, Salt Lake City, USA) agreed but pointed out that he has had “very few patients who are really enthusiastic about receiving chemotherapy.”
He continued: “When we have oral therapies that allow our patients to not receive chemotherapy and avoid steroids, it’s an enormous advance in my view.”
And we have results on two such therapies reported at this conference, Agarwal commented. “Both enzalutamide and apalutamide will allow my patients in the clinic to avoid chemotherapy, and that’s the message I am going to get from these two presentations.”
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