Patient-reported outcomes (PROs) in KEYNOTE-921: Pembrolizumab (pembro) plus docetaxel for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Petrylak Daniel P. , Ratta Raffaele , Matsubara Nobuaki , Korbenfeld Ernesto Pablo , Gafanov Rustem , Mourey Loic , Todenhöfer Tilman , Gurney Howard , Kramer Gero , Bergman Andre M. , Zalewski Pawel , De Santis Maria , Armstrong Andrew J. , Gerritsen Winald R. , Pachynski Russell Kent , Saretsky Todd L. , Ghate Sameer R. , Li Xin Tong , Schloss Charles , Fizazi Karim 
Published: March 2023

129 Background: The double-blind, phase 3, randomized KEYNOTE-921 trial (NCT03834506) showed that pembro + docetaxel did not significantly improve rPFS or OS for pts with mCRPC treated with prior next-generation hormonal agent (NHA) therapy. We present PROs for pembro + docetaxel vs placebo + docetaxel in KEYNOTE-921. Methods: Pts were randomly assigned 1:1 to receive pembro 200 mg or placebo IV Q3W (≤35 cycles) + docetaxel 75 mg/m2 IV Q3W (≤10 cycles) and prednisone 5 mg orally BID. PROs were evaluated in pts who received ≥1 dose of study treatment and had ≥1 PRO assessment. FACT-P and BPI-SF were administered at baseline, Q3W until wk 24, Q6W until wk 72, then Q12W for ≤2 y. A prespecified secondary end point was time to pain progression (TTPP) based on BPI-SF. Prespecified exploratory end points included least squares mean (LSM) change from baseline to wk 27 for FACT-P total and subscale scores (FACT-G total, TOI, FAPSI-6, FWB, PWB, and PCS) and wk 24 for BPI-SF scores (pain interference, pain severity, and worst pain), and time to deterioration (TTD) and overall improvement rate in FACT-P total and subscale scores. Differences were evaluated using 2-sided nominal P values not controlled for multiplicity. Results: Of 1030 pts enrolled, the PRO analysis population included 1028 (n = 514 in each arm). At the prespecified final analysis, median time from randomization to data cutoff of June 20, 2022, was 22.7 mo (range, 12.1-36.7). Completion rates for FACT-P and BPI-SF were >78% at baseline, >65% for FACT-P at wk 27, and >63% for BPI-SF at wk 24. Median TTPP was 21.1 mo (95% CI, 13.7-NR) for pembro + docetaxel vs NR (95% CI, 13.8-NR) for placebo + docetaxel (HR, 1.05 [95% CI, 0.77-1.43]). No LSM differences were observed in FACT-P total scores with pembro + docetaxel (–5.31 [95% CI, –7.02 to –3.61]) vs placebo + docetaxel (–3.89 [95% CI, –5.59 to –2.19]) or BPI-SF scores. Median TTD in FACT-P total scores was 21.8 mo (95% CI, 20.0-NR) for pembro + docetaxel and NR (95% CI, 11.1-NR) for placebo + docetaxel (HR, 1.09 [95% CI, 0.88-1.35]). No differences were observed for TTD in FACT-G total, TOI, FAPSI-6, FWB, PWB, and PCS scores between groups. A numerically lower proportion of pts receiving pembro + docetaxel (39.9%) had improved + stable FACT-P total scores compared with placebo + docetaxel (45.3%). FACT-P and BPI-SF scores were generally maintained across all evaluated time points up to wk 81. Conclusions: HRQoL and disease-related symptom scores at all analyzed time points, as well as TTD and TTPP, were similar between the 2 trial arms. These data suggest that pembro + docetaxel did not negatively impact QoL in pts with mCRPC treated with prior NHA. Clinical trial information: NCT03834506 . [Table: see text]