Enzalutamide prolonged survival and delayed radiographic progression of disease in men who had not received chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), according to complete results from the phase 3 PREVAIL trial.
An interim analysis in 2013 was so favorable that the trial was halted prematurely, and all patients receiving placebo were offered enzalutamide. The drug was approved by the US Food and Drug Administration (FDA) in 2012 for the treatment of patients with mCRPC who had received previous therapy.
“Enzalutamide provides clinically meaningful benefit for men with mCRPC. It is approved by the FDA in men previously treated with docetaxel, but not yet approved for use prior to docetaxel. If it does get expanded approval for this indication, it is likely to become an important standard option for use in patients with asymptomatic or minimally symptomatic advanced prostate cancer,” said lead author Tomasz Beer, MD, deputy director of the Knight Cancer Institute at Oregon Health & Science University, Portland, at the 2014 Genitourinary Cancers Symposium.
Between September 2010 and September 2012, PREVAIL included 1717 patients with asymptomatic or mildly symptomatic mCRPC who had not received previous chemotherapy. They were randomized to enzalutamide or to placebo plus standard hormone therapy.
For the coprimary end points of the trial—overall survival and radiographic progression-free survival—
enzalutamide reduced the risk of death by 29% (hazard ratio [HR] 0.70; P <.0001), and reduced the risk of radiographic progression by 81% (HR 0.19; P <.0001).
Overall response rate according to imaging of soft tissue disease was 59% with enzalutamide (20% complete responses and 39% partial responses) versus 5% with placebo (P <.0001).
Importantly, enzalutamide delayed the need for chemotherapy by a median of 28 months versus 10.8 months for placebo.
“This is important from a pragmatic perspective. Many men don’t want to take chemotherapy, especially if they are asymptomatic or mildly symptomatic,” Beer stated.
Safety observation was 3 times longer with enzalutamide, reflecting the longer duration of treatment in this arm, he continued. Enzalutamide was well tolerated after 17 months of treatment; the most common side effects (in 20% of patients) were fatigue (36% of enzalutamide patients, 26% of placebo patients), constipation (22% and 27%, respectively), back pain (27% and 22%, respectively), and joint pain (20% and 16%, respectively).
Grade 3 or higher adverse events were reported in 43% of the enzalutamide group versus 37% of the placebo group. Six percent of patients in both arms discontinued treatment due to adverse events.
Charles Ryan, MD, moderator of the press cast where these data were discussed, emphasized that this study breaks new ground for enzalutamide in chemotherapy-naive patients with mCRPC. “The interim analysis showed benefit in this patient group, and this is an impor-tant study in our field, to be sure,” Ryan noted.
Beer said that both abiraterone and enzalutamide have shown benefit in docetaxel-naive patients with metastatic disease, but at present there are no head-to-head comparisons to guide treatment selection. Decisions should be made on an individual patient basis, he stated.
Further studies comparing these treatments and sequencing them are needed, as well as studies earlier in the disease process, Beer noted.
Beer TM, Logothetis C, Gerritsen WR, et al. Characterization of immune-related adverse events (irAEs) in a phase 3 trial of ipilumumab (Ipi) versus placebo (Pbo) in post-docetaxel mCRPC. J Clin Oncol. 2014;32(suppl 4):Abstract 52. Presented at: 2014 Genitourinary Cancers Symposium; January 30-February 1, 2014; Orlando, FL.