Treatment with enzalutamide significantly extended OS and radiographic PFS in chemotherapy-naive men with metastatic castration-resistant prostate cancer compared with placebo, according to study results presented at the 2014 Genitourinary Cancers Symposium.
“The radiographic PFS and time-to-chemotherapy results are quite striking in this trial and represent the direct effect of therapy that’s not contaminated by subsequent treatments post-progression,” Tomasz M. Beer, MD, FACP, professor of medicine and deputy director of the Knight Cancer Institute at Oregon Health and Science University, said during a press conference. “The OS certainly is reassuring, but it incorporates into outcome the effects of subsequent therapy that these patients received.”
Tomasz M. Beer
Previous research indicated enzalutamide (Xtandi, Astellas Pharma) improved OS in men with metastatic castration-resistant prostate cancer who had received prior treatment with docetaxel.
In the double blind, phase 3 PREVAIL trial, Beer and colleagues sought to evaluate the agent in asymptomatic or mildly symptomatic men who had not received chemotherapy. They assigned 1,717 patients 1:1 to 160 mg enzalutamide daily or placebo.
Researchers conducted an interim analysis after 539 deaths occurred. At the time of analysis, more patients assigned placebo had died (35% vs. 28%).
Results showed enzalutamide was associated with a 30% reduction in the risk for death (HR=0.7; 95% CI, 0.59-0.83) and an 81% reduction in the risk for radiographic progression or death (HR=0.19; 95% CI, 0.15-0.23).
The estimated median OS in the enzalutamide arm was 32.4 months (95% CI, 31.5-upper limit not yet reached) compared with 30.2 months (95% CI, 28-upper limit not yet reached) in the placebo arm.
Median radiographic PFS had not yet been reached at the time of the analysis in the enzalutamide arm (95% CI, 13.8-upper limit not yet reached) but was 3.9 months (95% CI, 3.7-5.4 ) in the placebo arm.
Fifty-nine percent of patients assigned enzalutamide responded to treatment (complete response, 20%; partial response, 39%) compared with 5% of patients assigned placebo.
Researchers observed a 65%, or 17-month, increase in time to chemotherapy among patients who received enzalutamide compared with placebo.
The most common adverse events associated with treatment were fatigue, constipation, and back and joint pain. Two patients with a prior history of seizures — one from each arm — experienced seizure events.
“The concern was that, as we moved the drug into earlier disease states — like we did in this clinical trial — and as the duration of therapy lengthens, that some might see a higher rate of side effects, including seizures,” Beer said. “But the rate is actually lower than what we would have expected. With appropriate patient selection, this drug can be administered very safely from the perspective of seizure risk.”
Six percent of patients in both arms discontinued treatment due to adverse events.
The next step is to evaluate possible sequences and combinations of therapies, such as with abiraterone acetate (Zytiga, Janssen Biotech), Beer said.
“We have two new drugs — enzalutamide and abiraterone — that have emerged very rapidly and have been studied in phase 3 studies only in metastatic, advanced disease, and only in isolation from one another,” Beer said. “What these studies say is that not only do we have new treatment options, but they validate the notion that the hormonal signaling pathway is critically important in the management of prostate cancer. When you get new effective drugs in a disease, the work just begins. I think you’re going to see a continued evolution of how these drugs are used.”
For more information:
Beer TM. Abstract #LBA1. Presented at: 2014 Genitourinary Cancers Symposium; Jan. 30-Feb. 1, 2014; San Francisco.
Disclosure: Beer reports research funding from Astellas Pharma, Cougar Biotechnology, Janssen Biotech and Medivation. See the study for a full list of the researchers’ relevant financial disclosures.