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Enzalutamide improves OS for metastatic hormone-sensitive prostate cancer
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CHICAGO — Enzalutamide used in combination with standard therapy significantly improved OS compared with other nonsteroidal antiandrogen drugs for men with metastatic hormone-sensitive prostate cancer, according to results of the randomized phase 3 ENZAMET trial presented during the plenary session of ASCO Annual Meeting.
“Until 2014, testosterone suppression plus or minus standard nonsteroidal antiandrogen was the only therapy for metastatic hormone-sensitive prostate cancer,” Christopher Sweeney, MBBS, medical oncologist at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School, said during his presentation. “We knew patients with a higher burden of disease had shorter OS, and that was the state of affairs for about 70 years. Improvements in outcome performance emerged with the use of agents that were active in castration-resistant disease [with] docetaxel and abiraterone.”
Sweeney and colleagues hypothesized enzalutamide (Xtandi; Astellas, Pfizer), a potent androgen receptor inhibitor, added to testosterone suppression would improve OS with or without docetaxel — and more than with standard nonsteroidal antiandrogen (NSAA) medications — as first-line therapy for metastatic hormone-sensitive prostate cancer.
The researchers randomly assigned 1,125 men (median age, 69 years) to the standard therapy of testosterone-suppressing drugs — including goserelin (Zoladex; TerSera AstraZeneca), degarelix (Firmagon, Ferring Pharmaceuticals) and leuprolide — in combination with 160 mg oral enzalutamide daily (n = 563) or one of the three standard NSAAs : bicalutamide, nilutamide or flutamide (n = 562).
Among all patients, 503 received early doses of docetaxel, including 249 patients in the NSAA group and 254 patients in the enzalutamide group.
OS served as the primary endpoint. Secondary endpoints included PSA PFS, PFS and adverse events.
Median follow-up was 34 months.
Results showed that at 3 years, 80% of men who received enzalutamide remained alive compared with 72% of men who received one of the other three NSAAs (HR = 0.67, 95% CI, 0.52-0.86).
Overall, men who received enzalutamide had a 33% decreased risk for death compared with men who received other NSAAs.
Among 596 men with high-volume disease, 71% in the enzalutamide group were alive after 3 years compared with 64% who took another NSAA (HR = 0.74; 95% CI, 0.55-1.01).
Among 529 men with low volume disease, 90% in the enzalutamide group were alive after 3 years compared with 82% who took another NSAA (HR = 0.48; 95% CI, 0.28-0.8).
Men who did not receive early planned docetaxel demonstrated the greatest OS benefit. Results among those men showed 3-year OS of 83% with enzalutamide vs. 70% with other NSAAs.
Over half (64%) of men in the enzalutamide group were still on the drug after 3 years compared with 36% of men taking another NSAA.
Serious adverse events within 30 days of study treatment occurred among 42% of men in the enzalutamide group compared with 34% of men taking another NSAA.
Sweeney added that enzalutamide increased the docetaxel toxicity, which is something that must be reconciled.
“The clinical interpretation of this is that enzalutamide added to testosterone suppression represents an appropriate option for men with metastatic prostate cancer commencing testosterone suppression,” Sweeney said. “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 compounds prostate cancer therapy favorably and augments survival beyond 3 years.”– by John DeRosier
Reference:
Sweeney C, et al. Abstract LBA2. Presented at: ASCO Annual Meeting; May 31-June 4, 2019; Chicago.
Disclosures: Sweeney reports consultant/ advisory roles with or research funding from Amgen, Astellas Pharma, AstraZeneca, Bayer, Dendreon, Genentech/Roche, Janssen Biotech, Pfizer, Sanofi and Sotio, as well as stock ownership in Leuchemix. Please see the abstract for all other authors’ relevant financial disclosures.
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Matthew Zibelman, MD
Data from this trial confirm that we have another potential option for men with metastatic hormone-sensitive prostate cancer.
We knew that docetaxel and the combination of abiraterone and prednisone had demonstrated benefit, and it now appears we have a third option.
This will become a key option to add to androgen depletion therapy and improve survival, particularly among patients with asymptomatic low-volume disease, especially those with diabetes or contraindications to prednisone.
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