Astellas Pharma and Pfizer have announced that phase III results from the PROSPER trial of enzalutamide (Xtandi) in men with nonmetastatic castration-resistant prostate cancer (CRPC) will be ready later this year. Previously, those data weren’t scheduled for release until June 2019.
Astellas Pharma and Pfizer announced the protocol change June 12. This new protocol revises the planned analyses of the primary and several secondary endpoints, reducing the target patient population to 1440 patients, down from 1560.
A spokesperson for Astellas told OncLive
that “recent clinical results for enzalutamide in nonmetastatic and chemotherapy-naïve metastatic CRPC” have led investigators to believe that they could shrink the target sample size because they need fewer metastasis-free survival events to sufficiently power the study, and this should not have a negative effect on the strength of the data.
“We know more now than we did when the original study was designed and initiated in 2013,” Pfizer corporate spokesperson Sally Beatty said to OncLive.
“As the understanding of prostate cancer has evolved and other trials have demonstrated the overall survival benefit of Xtandi, we have better confidence to appropriately size the trial and evolve the protocol. As a result, upon the acquisition of Medivation, our Pfizer team worked with the Astellas team to identify the potential to amend the protocol and accelerate the timeline.”
Pfizer purchased Medivation, the original manufacturer of enzalutamide, in August 2016.
PROSPER is a multinational, randomized, double blind, placebo controlled trial evaluating the efficacy and safety of enzalutamide. The study was initiated in December 2013 at 287 locations and is scheduled to end in May 2020. Patients in the experimental arm are assigned to 160 mg daily of oral enzalutamide. The primary endpoint is metastatic-free survival and secondary endpoints include overall survival (OS), time to prostate-specific antigen progression, and time to chemotherapy-free survival.
Enzalutamide has been FDA-approved to treat late-stage CRPC for men previously treated with docetaxel since 2012. The agency approved the drug for first-line therapy in 2014 based on results from the phase III PREVAIL trial which showed that enzalutamide improved OS by 29% and radiographic progression-free survival (rPFS) by 81% compared with placebo.
In PREVAIL, 1717 men with a median age of 71 years received treatment with enzalutamide (n = 872) or placebo (n = 845). Enzalutamide was administered at 160 mg daily. An interim analysis was conducted following 540 deaths, which demonstrated a statistically significant advantage for enzalutamide for both OS and rPFS. At that point, the study was halted and men in the placebo arm were allowed to crossover to enzalutamide.
The agency expanded the drug’s label again last year based on results from the phase II TERRAIN trial. Those results showed that enzalutamide reduced the risk of radiographic progression or death by 40% compared with bicalutamide, and improved median rPFS by 6.1 months in patients with metastatic CRPC.
In TERRAIN, chemotherapy-naïve patients with metastatic CRPC (N = 375) were randomized to enzalutamide at 160 mg orally once daily or 50 mg of once-daily bicalutamide at 50 mg. Median rPFS was 19.5 months with enzalutamide compared with 13.4 months with bicalutamide (HR, 0.60; 95% CI, 0.43-0.83).
The safety data for enzalutamide was comparable to results reported from previous enzalutamide studies. The most common all-grade adverse events (AEs) with enzalutamide included asthenic conditions, back pain, musculoskeletal pain, hot flush, hypertension, diarrhea, upper respiratory tract infection, and weight loss.
Grade 3/4 AEs occurred in 38.8% and 37.6% of the enzalutamide and bicalutamide arms, respectively. Although most grade ≥3 AEs occurred at similar rates between the arms, there were a few exceptions: hypertension (7.1% in the enzalutamide arm vs 4.4% in the bicalutamide arm), diarrhea (0% vs 1.1%), and back pain (2.7% vs 1.6%). Seizures occurred in 2 patients in the enzalutamide group and 1 patient in the bicalutamide group.