As reported in the Journal of Clinical Oncology by Petrylak et al, the phase III KEYNOTE-921 trial showed no benefit in outcomes with the addition of pembrolizumab to docetaxel in patients with previously treated metastatic castration-resistant prostate cancer.
Study Details
In the global double-blind trial, 1,030 patients who experienced disease progression after androgen-deprivation therapy and one androgen receptor pathway inhibitor were randomly assigned between May 2019 and June 2021 to receive docetaxel at 75 mg/m2 every 3 weeks for up to 10 cycles with concomitant prednisone at 5 mg twice daily and either pembrolizumab at 200 mg (n = 515) or matched placebo (n = 515) every 3 weeks for up to 35 cycles. The primary endpoints were radiographic progression–free survival on blinded independent central review and overall survival.
Key Findings
Median time from random assignment to data cutoff date (in June 2022) at final analysis was 22.7 months (range = 12.1–36.7 months).
At first interim analysis (data cutoff date at the end of September 2021), median radiographic progression–free survival was 8.6 months (95% confidence interval [CI] = 8.3–10.2 months) in the pembrolizumab/docetaxel group vs 8.3 months (95% CI = 8.2–8.5 months) in the control group (hazard ratio [HR] = 0.85, 95% CI = 0.71–1.01, P = .03); since the difference did not reach the predefined significance level of P = .02, no further testing for radiographic progression–free survival was performed. Rates were 29.4% vs 23.8% at 12 months and 9.4% vs 6.5% at 18 months.
At final analysis, median overall survival was 19.6 months (95% CI = 18.2–20.9 months) in the pembrolizumab/docetaxel group vs 19.0 months (95% CI = 17.9–20.9 months) in the control group (HR= 0.92, 95% CI = 0.78–1.09, P = .17). Rates were 76.9% vs 73.2% at 12 months and 39.4% vs 38.5% at 24 months.
Grade ≥3 treatment-related adverse events occurred in 43.2% of the pembrolizumab/docetaxel group and 36.6% of the control group; the most common in each group were diarrhea (3.3% vs 1.9%), fatigue (2.7% vs 3.1%), and anemia (2.7% vs 3.3%). Any-grade pneumonitis was the most common immune-mediated adverse event (7.0% vs 3.1%). Treatment-related serious advents occurred in 20.2% vs 15.2% of patients. Treatment-related death occurred in two patients in the pembrolizumab/docetaxel group (from pneumonitis and interstitial lung disease) and seven patients in the control group (from clostridial sepsis, febrile neutropenia, influenzal pneumonia, neck abscess, pneumonia, respiratory failure, and urosepsis).
The investigators concluded: “The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated [metastatic castration-resistant prostate cancer]. The current standard of care remains unchanged.”
Daniel P. Petrylak, MD, of Yale Cancer Center, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. For full disclosures of the study authors, visit ascopubs.org.
