Dr. Petrylak on Results From the KEYNOTE-921 Trial of Pembrolizumab Plus Docetaxel in mCRPC

Daniel P. Petrylak, MD, professor of medicine and urology, coleader, Cancer Signaling Networks, Yale Cancer Center, discusses efficacy and safety data from the phase 3 KEYNOTE-921 trial (NCT03834506) of pembrolizumab (Keytruda) and docetaxel in metastatic castrate-resistant prostate cancer (mCRPC).

The rationale for exploring this combination was that cellular damage caused by docetaxel increases the susceptibility of prostate cancer cells to immune attack, which could then be heightened with the addition of an immunotherapy agent, Petrylak begins. Prior data from cohort B of the phase 1b/2 KEYNOTE-365 trial (NCT02861573) showed that docetaxel and pembrolizumab generated responses as well as radiographic progression-free survival (rPFS) and overall survival (OS), Petylak adds.

Based on these findings, the randomized, double-blind, KEYNOTE-921 study was designed, Petrylak says. It aimed to improve on the efficacy of standard chemotherapy in patients with mCRPC following disease progression on androgen-deprivation therapy (ADT) and a next-generation hormonal agent (NHA), he continues.

Patients in KEYNOTE-921 randomly assigned to either pembrolizumab plus docetaxel and prednisone or placebo plus docetaxel and prednisone.

The trial did not meet its dual primary end points of rPFS and OS. Although the combination did elicit numerical increases in OS and rPFS, these improvements were not statistically significant, Petrylak states. Results showed that median OS was 19.6 months in the pembrolizumab arm and 19.0 months in the placebo arm. The median rPFS was 9.6 months for the pembrolizumab arm and 9.3 months for the placebo arm. Additionally, no statistically significant difference was observed with secondary end points, such as objective response rate and time to next treatment, Petrylak says.

Safety analysis provided similar results, with treatment-related adverse effects (TRAEs) occurring in 94.6% and 94.9% of patients in the combination and control arms, respectively. Toxicity profiles were consistent with previous studies. However, immune-mediated AEs and infusion reactions were numerically higher with the pembrolizumab regimen, and the addition of pembrolizumab appeared to have an additive effect on the rate of pneumonitis compared with each individual agent, Petrylak notes.

Overall, these findings indicate that docetaxel alone should remain the standard of care in mCRPC following progression on an NHA, Petrylak concludes.

Editor’s Note: Dr. Petrylak reports serving as a consultant or in an advisory role for Advanced Accelerator Applications, Amgen, Astellas Pharma, AstraZeneca, Bayer, Bicycle Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Clovis Oncology, Exelixis, Gilead Sciences, Incyte, Ipsen, Janssen, Loxo/Lilly, Mirati Therapeutics, Monopteros Therapeutics, Pfizer, Pharmacyclics, Regeneron, Roche, Seagen, Urogen pharma; he reports institutional research funding from Advanced Accelerator Applications, Agensy, Astellas Pharma, AstraZeneca, Bayer, BioXCel Therapeutics, Bristol-Myers Squibb, Clovis Oncology, Eisai, Endocyte, Genentech, Gilead Sciences, Innocrin Pharma, Loxo/Lilly, MedImmune, Medivation, Merck, Mirati Therapeutics, Novartis, Pfizer, Progenics, Replimune, Roche, Sanofi, Seagen; he has provided expert testimony for Celgene and Sanofi.