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Enzalutamide superior to bicalutamide for castration-resistant prostate cancer
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The oral androgen receptor inhibitor enzalutamide significantly reduced the risk for prostate cancer progression or death compared with bicalutamide in patients with castration-resistant prostate cancer, according to findings from the STRIVE trial.
Enzalutamide (Xtandi, Astellas) has been found to improve survival in men with castration-resistant prostate cancer prior to and following chemotherapy. It binds the androgen receptor in the same way as bicalutamide does, but with greater affinity, according to researchers.
Since bicalutamide is the standard treatment for this population of patients, researchers conducted this phase 2 trial to compare the two treatments.
“The thing that surprised me the most about the results of STRIVE was the magnitude of benefit seen in the enzalutamide arm,” David F. Penson, MD, MPH, chair of the department of urologic surgery and the Paul V. Hamilton, MD and Virginia E. Howd professor of urologic oncology at Vanderbilt-Ingram Cancer Center in Nashville, told HemOnc Today. “I expected it to be better than bicalutamide, but not to this extent. The marked degree of benefit and the fact that, in every subgroup analysis, the findings were consistently positive was really eye-opening for me.
“Many prostate cancer specialists currently will initiate bicalutamide in patients who are newly castrate resistant on androgen deprivation monotherapy,” Penson added. “STRIVE really indicates that we may be doing our patients a disservice with this approach.”
PFS served as the study’s primary endpoint. Secondary endpoints included time to PSA progression, a PSA response of 50% or greater, and radiographic PFS for patients with metastatic disease only.
The analysis included 396 men with nonmetastatic (n = 139) or metastatic (n = 257) castrate-resistant prostate cancer.
Researchers randomly assigned patients to receive 160 mg daily enzalutamide (n = 198; median age, 72 years) or 50 mg daily bicalutamide (n = 198; median age, 74 years).
Median treatment time was 14.7 months in the enzalutamide arm and 8.4 months in the bicalutamide arm. Further, more patients in the enzalutamide arm received at least 12 months of treatment (68% vs. 35%).
Overall, enzalutamide reduced the risk for progression or death 76% (HR = 0.24; 95% CI, 0.18-0.32) compared with bicalutamide.
Patients who received enzalutamide achieved a median PFS of 19.4 months (95% CI, 16.5-not yet reached), whereas median PFS was 5.7 months (95% CI, 5.6-8.1) for bicalutamide.
Researchers noted the improvement in PFS with enzalutamide persisted across patient subgroups, including disease state. Median PFS improved with enzalutamide among men with nonmetastatic (not reached vs. 8.6 months; HR = 0.24; 95% CI, 0.14-0.42) and metastatic disease (16.5 months vs. 5.5 months; HR = 0.24; 95% CI, 0.17-0.34).
“The other interesting thing about STRIVE is the M0 subgroup analysis,” Penson said. “Again, enzalutamide was clearly superior to bicalutamide in these patients. Now, this is a subgroup analysis in a phase 2 study, so we shouldn’t be changing practice based on these findings, but it is still very thought provoking.
Enzalutamide demonstrated significant improvements regarding all of the study’s secondary endpoints. Researchers observed an 81% reduction in time to PSA progression (HR = 0.19; 95% CI, 0.14-0.26), as well as reductions in the risk for radiographic progression or death among men with metastatic (HR = 0.32; 95% CI, 0.21-0.5) and nonmetastatic disease (HR = 0.24; 95% CI, 0.1-0.56) with enzalutamide.
Further, a greater proportion of patients on the enzalutamide arm achieved a PSA response of at least 50% (81% vs. 31%; P < .001).
The safety profile of enzalutamide appeared consistent with previously reported results from phase 3 enzalutamide trials. Thirty-six percent of men who received enzalutamide experienced an adverse event of grade 3 or worse — which was the same rate of adverse events that occurred on the bicalutamide arm — with the most common being fatigue (5%), hypertension (5%) and anemia (3%).
Limitations of the study included that the benefit of sequential therapy with bicalutamide followed by enzalutamide was not addressed and the trial was not designed to assess OS as an endpoint, according to the researchers.
“There is currently a phase 3 study ongoing in M0 patients exploring the effectiveness of enzalutamide and, if STRIVE is any sort of guide, I expect that study will be positive and we will then be using enzalutamide in M0 patients,” Penson said. – by Anthony SanFilippo
For more information:
David F. Penson, MD, MPH, can be reached at david.penson@vanderbilt.edu.
Disclosure: Penson reports consultant/advisory roles with and research funding from Astellas Pharma and Medivation. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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