KEYNOTE-921
Trial question
What is the role of addition of pembrolizumab to docetaxel in patients with previously treated metastatic castration-resistant prostate cancer?
Study design
Multi-center
Double blinded
RCT
Population
1030 male patients.
Inclusion criteria: adult patients with metastatic castration-resistant prostate cancer who progressed after androgen-deprivation therapy and one androgen receptor pathway inhibitor therapy.
Key exclusion criteria: previous radium or radiopharmaceuticals; known additional malignancy that is progressing or has required active treatment in the last 3 years; active autoimmune disease that has required systemic treatment in the past 2 years; immunodeficient state or receipt of chronic systemic corticosteroid therapy; active infection requiring systemic therapy; history of pneumonitis that required corticosteroids or current pneumonitis.
Interventions
N=515 pembrolizumab plus docetaxel (pembrolizumab 200 mg IV every 3 weeks for ≤ 35 cycles plus docetaxel 75 mg/m² IV every 3 weeks for ≤ 10 cycles with concomitant prednisone 5 mg PO BID).
N=515 placebo plus docetaxel (matching placebo IV every 3 weeks for ≤ 35 cycles plus docetaxel 75 mg/m² IV every 3 weeks for ≤ 10 cycles with concomitant prednisone 5 mg PO BID).
Primary outcome
Median radiographic progression-free survival
8.6 months
8.3 months
8.6 months
6.4 months
4.3 months
2.1 months
0.0 months
Pembrolizumab plus
docetaxel
Placebo plus
docetaxel
No significant
difference ↔
No significant difference in median radiographic progression-free survival (8.6 months vs. 8.3 months; HR 1.18, 95% CI 0.99 to 1.41).
Secondary outcomes
No significant difference in median overall survival (19.6 months vs. 19 months; HR 1.09, 95% CI 0.92 to 1.28).
No significant difference in median time to initiation of the first subsequent anticancer therapy (10.7 months vs. 10.4 months; HR 1.16, 95% CI 0.99 to 1.35).
No significant difference in median time to PSA progression (6.9 months vs. 7 months; HR 0.96, 96% CI 0.82 to 1.12).
Safety outcomes
No significant differences in adverse events, treatment-related adverse events.
Conclusion
In adult patients with metastatic castration-resistant prostate cancer who progressed after androgen-deprivation therapy and one androgen receptor pathway inhibitor therapy, pembrolizumab plus docetaxel was not superior to placebo plus docetaxel with respect to median radiographic progression-free survival.
Reference
Daniel P Petrylak, Raffaele Ratta, Nobuaki Matsubara 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. 2025 Mar 5:JCO2401283. Online ahead of print.
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