Pembrolizumab for advanced anal squamous cell carcinoma (ASCC): Results from the multicohort, phase II KEYNOTE-158 study.
Bibliographic record
Abstract
1 Background: For patients (pts) with ASCC, second-line or later treatment options have been limited. Pembrolizumab (pembro), an anti-PD-1 monoclonal antibody, has demonstrated antitumor activity in several tumor types (including ASCC) in the multicohort phase 1b KEYNOTE-028 study. KEYNOTE-158 (NCT02628067) is an open-label, phase 2, multicohort study that evaluates antitumor activity and safety of pembro in pts with previously treated advanced cancer. Results from the ASCC cohort are presented. Methods: Eligible pts were ≥18 y with histologically/cytologically documented metastatic and/or unresectable ASCC with prior treatment failure on or intolerance to standard first-line therapy, measurable disease per RECIST v1.1, ECOG PS of ≤1, and evaluable tissue sample for PD-L1 and biomarker analysis. PD-L1 expression was assessed by the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies). Pts received pembro 200 mg Q3W until disease progression, unacceptable AE, or completion of 35 cycles. The primary endpoint was ORR per RECIST v1.1 (assessed every 9 wk for 12 mo, then every 12 wk thereafter) by independent central review. Secondary endpoints were DOR, OS, PFS and safety. Results: 112 pts with ASCC were enrolled (81.3% women; median age, 61 y [range 32–79]; ≥2 prior therapies, 73.2%). At database cutoff (Dec 6, 2018) 10 pts (8.9%) had completed 35 cycles and 102 discontinued; median follow-up was 12.0 mo (range, 0.8–33.0) Five pts had CR and 8 had PR; ORR was 11.6% (95% CI, 6.3–19.0). Median DOR was not reached (range, 6.0+ to 29.1+ mo). Responses occurred in 11/75 pts (14.7%) with PD-L1 combined positive score (CPS) ≥1 and 2/30 pts (6.7%) with PD-L1 CPS < 1. Among all pts, median OS was 12.0 mo (95% CI, 9.1–15.4), and median PFS was 2.0 mo (95% CI, 2.0–2.1). 68 (60.7%) pts had treatment-related AEs, including 21 (18.8%) who had grade 3–5 events; there were no treatment-related deaths. 4 pts (3.6%) discontinued due to treatment-related AEs. 27 pts (24.1%) had immune-mediated AEs/infusion reactions. Conclusions: Pembro demonstrated antitumor activity and manageable toxicity in pts with heavily pretreated advanced ASCC, regardless of PD-L1 status. Clinical trial information: NCT02628067.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
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".