TY - JOUR
T1 - Pembrolizumab Plus Docetaxel Versus Docetaxel for Previously Treated Metastatic Castration-Resistant Prostate Cancer
T2 - The Randomized, Double-Blind, Phase III KEYNOTE-921 Trial
AU - Petrylak, Daniel P.
AU - Ratta, Raffaele
AU - Matsubara, Nobuaki
AU - Korbenfeld, Ernesto
AU - Gafanov, Rustem
AU - Mourey, Loic
AU - Todenhöfer, Tilman
AU - Gurney, Howard
AU - Kramer, Gero
AU - Bergman, Andries M.
AU - Zalewski, Pawel
AU - De Santis, Maria
AU - Armstrong, Andrew J.
AU - Gerritsen, Winald
AU - Pachynski, Russell
AU - Byun, Seok Soo
AU - Retz, Margitta
AU - Levesque, Eric
AU - McDermott, Ray
AU - Bracarda, Sergio
AU - Manneh, Ray
AU - Levartovsky, Meital
AU - Li, Xin Tong
AU - Schloss, Charles
AU - Poehlein, Christian H.
AU - Fizazi, Karim
N1 - Publisher Copyright:
© 2025 by American Society of Clinical Oncology.
PY - 2025/5/10
Y1 - 2025/5/10
N2 - PURPOSE The standard of care for metastatic castration-resistant prostate cancer (mCRPC) after second-generation androgen receptor pathway inhibitor (ARPI) therapy is still docetaxel. The randomized, double-blind, phase III KEYNOTE-921 trial (Clinicaltrials.gov identifier: NCT03834506) evaluated the efficacy and safety of pembrolizumab or placebo plus docetaxel for previously treated mCRPC. METHODS Adults with mCRPC who progressed after androgen-deprivation therapy and one ARPI were randomly assigned 1:1 to pembrolizumab or placebo plus docetaxel with concomitant prednisone. Dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group 3–modified RECIST 1.1 and overall survival (OS). Safety was a secondary end point. RESULTS Between May 30, 2019, and June 17, 2021, 515 participants were randomly assigned to pembrolizumab plus docetaxel and 515 to placebo plus docetaxel. Median time from random assignment to data cutoff date (June 20, 2022) at final analysis (FA) was 22.7 months (range, 12.1-36.7). At first interim analysis (data cutoff date: September 27, 2021), median rPFS was 8.6 months (95% CI, 8.3 to 10.2) with pembrolizumab plus docetaxel versus 8.3 months (95% CI, 8.2 to 8.5) with placebo plus docetaxel (hazard ratio [HR], 0.85 [95% CI, 0.71 to 1.01]; P 5 .03). At FA, median OS was 19.6 months (95% CI, 18.2 to 20.9) versus 19.0 months (95% CI, 17.9 to 20.9), respectively (HR, 0.92 [95% CI, 0.78 to 1.09]; P 5 .17). Grade ≥3 treatment-related adverse events occurred in 43.2% of participants who received pembrolizumab plus docetaxel and 36.6% of participants who received placebo plus docetaxel. Two and seven participants, respectively, died due to a treatment-related adverse event. Pneumonitis was the most common immune-mediated adverse event (7.0% v 3.1%). CONCLUSION The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC. The current standard of care remains unchanged.
AB - PURPOSE The standard of care for metastatic castration-resistant prostate cancer (mCRPC) after second-generation androgen receptor pathway inhibitor (ARPI) therapy is still docetaxel. The randomized, double-blind, phase III KEYNOTE-921 trial (Clinicaltrials.gov identifier: NCT03834506) evaluated the efficacy and safety of pembrolizumab or placebo plus docetaxel for previously treated mCRPC. METHODS Adults with mCRPC who progressed after androgen-deprivation therapy and one ARPI were randomly assigned 1:1 to pembrolizumab or placebo plus docetaxel with concomitant prednisone. Dual primary end points were radiographic progression-free survival (rPFS) by blinded independent central review per Prostate Cancer Working Group 3–modified RECIST 1.1 and overall survival (OS). Safety was a secondary end point. RESULTS Between May 30, 2019, and June 17, 2021, 515 participants were randomly assigned to pembrolizumab plus docetaxel and 515 to placebo plus docetaxel. Median time from random assignment to data cutoff date (June 20, 2022) at final analysis (FA) was 22.7 months (range, 12.1-36.7). At first interim analysis (data cutoff date: September 27, 2021), median rPFS was 8.6 months (95% CI, 8.3 to 10.2) with pembrolizumab plus docetaxel versus 8.3 months (95% CI, 8.2 to 8.5) with placebo plus docetaxel (hazard ratio [HR], 0.85 [95% CI, 0.71 to 1.01]; P 5 .03). At FA, median OS was 19.6 months (95% CI, 18.2 to 20.9) versus 19.0 months (95% CI, 17.9 to 20.9), respectively (HR, 0.92 [95% CI, 0.78 to 1.09]; P 5 .17). Grade ≥3 treatment-related adverse events occurred in 43.2% of participants who received pembrolizumab plus docetaxel and 36.6% of participants who received placebo plus docetaxel. Two and seven participants, respectively, died due to a treatment-related adverse event. Pneumonitis was the most common immune-mediated adverse event (7.0% v 3.1%). CONCLUSION The addition of pembrolizumab to docetaxel did not significantly improve efficacy outcomes for participants with previously treated mCRPC. The current standard of care remains unchanged.
UR - https://www.scopus.com/pages/publications/105000242152
U2 - 10.1200/JCO-24-01283
DO - 10.1200/JCO-24-01283
M3 - Article
C2 - 40043230
AN - SCOPUS:105000242152
SN - 0732-183X
VL - 43
SP - 1638
EP - 1649
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 14
ER -