Pembrolizumab (pembro) plus docetaxel and prednisone in patients (pts) with abiraterone acetate (abi) or enzalutamide (enza)-pretreated metastatic castration-resistant prostate cancer (mCRPC): KEYNOTE-365 cohort B efficacy, safety and, biomarker results.
Bibliographic record
Abstract
5550 Background: Pembro + docetaxel and prednisone (cohort B) has shown antitumor activity in pts with mCRPC in the phase I/II KEYNOTE-365 study (NCT02861573). Updated efficacy and safety and new biomarker data from cohort B are reported. Methods: Pts who received at least 4 wk of abi or enza in the prechemotherapy mCRPC setting and whose disease progressed within 6 mo of screening were eligible. Pts received pembro 200 mg IV + docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg orally twice daily. Primary end points were PSA response rate (PSA decrease ≥50%; confirmed by a second value ≥3 weeks later), ORR per RECIST v1.1 by blinded independent central review, and safety. Key secondary end points were DCR per RECIST v1.1 (CR+PR+SD or non-CR/non-PD ≥6 mo), DOR per RECIST v1.1, radiographic PFS (rPFS) per PCWG-modified RECIST, and OS. Biospecimens (blood, tissue) were collected for biomarker analysis, including tissue PD-L1 expression, androgen receptor variant 7 (AR-v7) expression in circulating tumor cells, and a T-cell-inflamed gene expression profile (GEP). Results: Of 105 enrolled pts, 104 were treated, and 50% had measurable disease. Median (range) time from enrollment to data cutoff was 19.9 mo (1.4-27.8) for all pts and 21.8 mo (17.9-27.8) for pts with ≥27 wks follow-up (n=72). Confirmed PSA response rate was 28% in 103 pts with a baseline PSA assessment. Median time to PSA progression was 6.2 mo (95% CI, 3.7-7.4). In pts with measurable disease and ≥27 wks follow-up (n=39), ORR was 18% (7/39, all PRs) and DCR was 51%. Median DOR was 6.7 mo (range, 3.4-9.0+ [+ indicates ongoing responder]); 5 pts had a response for ≥6 mo. In all pts, median rPFS was 8.3 mo (95% CI, 7.6-10.1) and OS was 20.4 mo (16.9-NR). At 6 mo, the rPFS rate was 72.8% and OS rate was 95.3%. Treatment-related AEs (TRAEs) occurred in 96% of all pts; most frequent were alopecia (39%), diarrhea (38%), and fatigue (38%). Grade 3-5 TRAEs occurred in 40% of pts; 2 pts died of TRAEs (pneumonitis). Overall, 24% of pts were PD-L1+ (combined positive score ≥1). Of 57 pts with AR-v7 data, 17.5% were AR-v7+, 77% were AR-v7−, and 5% were undetermined. GEP was not significantly associated with ORR or PSA response. Conclusions: Pembro + docetaxel and prednisone showed activity in pts with abi or enza-pretreated mCRPC. Safety of the combination was consistent with the known profiles of the individual agents. A phase 3 study of this combination is ongoing (KEYNOTE-921, NCT03834506). Clinical trial information: NCT02861573 .
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".