Pembrolizumab plus docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC): Randomized, double-blind, phase 3 KEYNOTE-921 study.
Bibliographic record
Abstract
19 Background: Docetaxel is a treatment option following disease progression on a next-generation hormonal agent (NHA) for patients with mCRPC, but there is an urgent need for more efficacious treatments. The randomized, double-blind, phase 3 KEYNOTE-921 study (NCT03834506) evaluated the efficacy and safety of pembrolizumab + docetaxel vs placebo + docetaxel for participants (pts) with mCRPC who had received prior NHA therapy. Methods: Eligible pts were ≥18 years old, had mCRPC that progressed on androgen deprivation therapy, had received 1 prior NHA, and had an ECOG performance status of 0 or 1. Pts were randomized 1:1 to receive 200 mg pembrolizumab Q3W or placebo for ≤35 cycles (~2 years) in combination with 75 mg/m2 docetaxel Q3W for ≤10 cycles and 5 mg prednisone BID. The dual primary endpoints were radiographic progression-free survival (rPFS; tested at first interim analysis) per PCWG-modified RECIST 1.1 by blinded independent central review and overall survival (OS; tested at final analysis). The key secondary endpoint was time to initiation of the first subsequent anticancer therapy (TFST; at first interim analysis). Safety was one of the secondary endpoints. Results: Between May 30, 2019 and June 17, 2021, 1030 pts were randomized to receive pembrolizumab + docetaxel (n=515) or placebo + docetaxel (n=515). The median (range) time from randomization to data cutoff date of June 20, 2022 at final analysis was 22.7 mo (12.1−36.7). Baseline characteristics were generally balanced between arms; approximately half of pts in each arm had received prior abiraterone. Pts in the pembrolizumab + docetaxel arm received a median (range) of 12 (1–35) cycles of pembrolizumab and 9 (1–12) cycles of docetaxel; pts in the placebo + docetaxel arm received a median (range) of 12 (1–35) cycles of placebo and 9 (1–10) cycles of docetaxel. The dual primary endpoints of rPFS (median 8.6 mo with pembrolizumab + docetaxel vs 8.3 mo with placebo + docetaxel; HR 0.85, 95% CI 0.71−1.01; P=0.0335) and OS (median 19.6 mo vs 19.0 mo; HR 0.92, 95% CI 0.78−1.09; P=0.1677) were not met. Median TFST was 10.7 mo vs 10.4 mo, respectively (HR 0.86, 95% CI 0.74−1.01). Treatment-related AEs occurred in 94.6% (grade ≥3 in 43.2%) and 94.9% (grade ≥3 in 36.6%) of pts with pembrolizumab + docetaxel vs placebo + docetaxel. 2 treatment-related deaths with pembrolizumab + docetaxel and 7 with placebo + docetaxel were reported. Immune-mediated AEs and infusion reactions occurred in 23.3% (grade ≥3 in 6.2%) and 12.3% (grade ≥3 in 1.2%) of pts with pembrolizumab + docetaxel vs placebo + docetaxel, most commonly pneumonitis (7.0% vs 3.1%) and hypothyroidism (6.4% vs 3.3%). Conclusions: The addition of pembrolizumab to docetaxel did not significantly improve rPFS or OS for pts with mCRPC and did not result in a notable increase in treatment-related AEs. Clinical trial information: NCT03834506 .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.002 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.010 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".