Delays need for chemotherapy in asymptomatic patients
San Francisco, CA—Enzalutamide (Xtandi) prolonged survival and delayed radiographic progression of disease in men who had not received chemotherapy for metastatic castration-resistant prostate cancer (mCRPC). The complete results of the phase 3 PREVAIL trial were presented at the 2014 Genitourinary Cancers Symposium.
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 2013 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 investigator Tomasz M. Beer, MD, Deputy Director, Knight Cancer Institute, Oregon Health and Science University, Portland.
Between September 2010 and September 2012, the PREVAIL trial 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 between September 2010 and September 2012.
For the coprimary end points of the trial—reduced mortality and radiographic disease progression—enzalutamide reduced the risk of death (ie, improved survival) by 29% (hazard ratio [HR], 0.76; P <.001) and the risk for radiographic disease progression by 81% (HR, 0.86; P <.001).
Enzalutamide slowed or halted tumor growth in 59% of the patients, based on the overall response rate (using imaging of soft-tissue disease), totally 20% complete responses and 39% partial responses compared with 5% response in the placebo group (P <.001).
Of note, enzalutamide delayed the need for chemotherapy by a median of 17 months: the median time to chemotherapy was 28 months in the enzalutamide group versus 10.8 months in the placebo arm (HR, 0.35; P <.001).
“This is important from a pragmatic perspective. Many men don’t want to take chemotherapy, especially if they are asymptomatic or mildly symptomatic,” Dr Beer emphasized.
Charles J. Ryan, MD, Associate Professor of Clinical Medicine, Helen Diller Family Comprehen-sive Cancer Center, University of California, San Francisco, the moderator of the press cast where these data were discussed, emphasized that this study breaks new ground for enzalutamide in chemotherapy-naïve patients with mCRPC. “The interim analysis showed benefit in this patient group, and this is an important study in our field,
to be sure,” Dr Ryan said.
Dr Beer said that abiraterone (Zytiga) and enzalutamide have shown benefit in docetaxel-naïve 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 advised.
The safety observation was 3 times longer with enzalutamide, reflecting longer duration of treatment in this arm, he continued. Enzalutamide was well tolerated after 17 months of treatment, with the most common adverse events (AEs; seen in ≥20% of patients) reported included fatigue (36% with enzalutamide vs 26% with placebo), constipation (22% vs 27%, respectively), back pain (27% vs 22%, respectively), and joint pain (20% vs 16%, respectively).
Grade ≥3 AEs were reported in 43% of the enzalutamide group versus 37% of the placebo group. In both arms, 6% of patients discontinued treatment because of AEs.
Further studies comparing these treatments and sequencing them are needed, as well as studies earlier in the disease process, Dr Beer noted.