ORLANDO – Treatment with enzalutamide significantly improved survival and radiographic progression-free survival in men with chemotherapy-naive metastatic prostate cancer – including those with visceral disease – according to a subgroup analysis of the randomized, double-blind PREVAIL study.
Of 1,717 patients in the study, 204 had visceral disease at screening, including 130 with lung disease and 74 with lung disease and/or liver disease. Those without visceral disease had lower baseline median prostate-specific antigen levels (46.8 vs. 72.5 ng/mL), better performance status (68.9 vs. 61.8%), and less lymph node disease (49.8% vs. 57.8%), than those with visceral disease, but the two groups had similar rates of bone disease (83.7% and 80.4%), Dr. Christopher Evans reported during a late-breaking abstract session at the annual meeting of the American Urological Association.
"That patients with visceral disease were included in the study is very important, as other studies have excluded patients with visceral disease," Dr. Evans said.
Overall survival in the PREVAIL study, as reported at the American Society of Clinical Oncology Genitourinary Cancers Symposium in February and online June 1 in the New England Journal of Medicine (N. Engl. J. Med. 2014 June 1 [doi:10.1056/NEJMoa1405095]), was significantly better in patients who received enzalutamide, compared with those who received placebo (32.4 vs. 30.2 months; hazard ratio, 0.71). In the current subgroup analysis comparing those with and without visceral disease, overall survival in those with visceral disease was 27.8 months and 22.8 months in the treatment and placebo groups, respectively (hazard ratio, 0.82). In those without visceral disease, the median time to death was not yet reached, said Dr. Evans of the department of urology, University of California Davis Health System, Sacramento.
Median radiographic progression-free survival duration in those with visceral disease was not yet reached in the treatment group and was 3.6 months in the placebo group, and in those without visceral disease it was 14.1 vs. 4.0 months with treatment vs. placebo (hazard ratio, 0.18), he said.
Additionally, patients without visceral disease, who may be more likely to be seen in the urologist’s office, were much less likely to use a subsequent life-extending therapy (typically docetaxel) if they received enzalutamide treatment rather than placebo (40% vs. 70%), Dr. Evans noted.
In a post hoc analysis, the secondary endpoint of time to cytotoxic chemotherapy was 28 vs. 10.8 months overall in the treatment vs. placebo group (HR, 0.35), 22.6 vs. 6.6 months for treatment vs. placebo in those with visceral disease (HR, 0.30), and 28.4 vs. 11.6 months for treatment vs. placebo in those without visceral disease (HR, 0.36).
"These curves are similar again in the visceral and nonvisceral subgroups. However, if we look at the placebo subgroup in the intention-to-treat population, we can see that median time to initiation of chemotherapy is 12 months. This is similar in the nonvisceral sub group, but is 6.5 months in the visceral subgroup – again showing that these patients have worse disease burden," he said.
In the intention-to-treat population, there was an 18-month improvement overall in the time to initiation of chemotherapy, giving urologists an opportunity to get involved in the treatment of these patients, he added.
The PREVAIL study examined the impact of oral enzalutamide (160 mg/day, compared with placebo, in asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic prostate cancer. The study, which was conducted at 207 centers in 22 countries between September 2010 and September 2012, was stopped at an interim analysis based on the significant survival benefits seen in the enzalutamide-treated patients. The current subgroup analysis demonstrates that although patients with visceral disease progressed more rapidly regardless of treatment allocation, the benefit of enzalutamide was consistent among patients with or without visceral disease.
Dr. Evans disclosed relationships with Amgen, Astellas, Medivation, Janssen, and Oncogenex, and investment interests in Medivation and Oncogenex.