Adding Pembrolizumab to Docetaxel Does Not Improve Survival Outcomes for Metastatic Castration-Resistant Prostate Cancer

According to results from the phase 3 KEYNOTE-921 trial, the addition of pembrolizumab to docetaxel did not significantly improve efficacy among previously treated patients with metastatic castration-resistant prostate cancer (mCRPC). 

While “immune checkpoint inhibitors have shown nominal antitumor activity in advanced prostate cancer,” wrote Daniel Petrylak, MD, Yale Cancer Center, New Haven, Connecticut, and coauthors, “no checkpoint inhibitor–based combination has yet been identified as superior to the standard of care in a randomized trial setting for mCRPC.” The KEYNOTE-921 study aimed to evaluate the addition of pembrolizumab to docetaxel for patients mCRPC after receiving previous androgen receptor pathway inhibitor (ARPI) therapy.

This double-blind, placebo-controlled trial enrolled patients with metastatic castration-resistant prostate cancer who experienced disease progression after androgen deprivation therapy and androgen receptor pathway inhibitor therapy. Patients were randomized on a 1-to-1 basis to receive either pembrolizumab (n = 515) or placebo (n = 515) plus docetaxel and concomitant prednisone. Primary end points included radiographic progression-free survival (rPFS) and overall survival (OS). A key secondary end point was safety. 

At a median follow-up of 22.7 months, median rPFS was 8.6 months in the pembrolizumab arm and 8.3 months in the placebo arm (hazard ratio [HR] 0.85; 95% confidence interval [CI], 0.71 to 1.01; P = .03). Median OS was 19.6 months and 19.0 months (HR, 0.92; 95% CI, 0.78 to 1.09; P = .17), respectively. Grade ≥3 treatment-related adverse events occurred in 43.2% of patients in the pembrolizumab arm and 36.6% of patients in the placebo arm. Treatment-related adverse events led to death in 2 patients in the pembrolizumab arm and 7 patients in the placebo arm. The most common immune-mediated adverse event was pneumonitis. 

“The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC,” concluded Dr Petrylak et al. “The current standard of care remains unchanged.” 

Journal of Clinical Oncology associate editor Andrea Necchi, MD, San Raffaele Hospital and Scientific Institute, Milan, Italy commented, “Taxane chemotherapy is unable to sensitize prostate cancer to immune checkpoint inhibitors, resulting in another negative trial with immunotherapy in prostate cancer. Further trials with immune checkpoint inhibitors in unselected patients should be discouraged.”

Source: 

Petrylak DP, Ratta R, Matsubara N, et al. Pembrolizumab plus docetaxel versus docetaxel for previously treated metastatic castration-resistant prostate cancer: The randomized, double-blind, phase III KEYNOTE-921 trial. J Clin Oncol. Published online: March 5, 2025. doi: 10.1200/JCO-24-01283