Pembrolizumab (P) or P + chemotherapy (C) versus EXTREME (E) as first-line (1L) therapy for recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): analysis of KEYNOTE-048 by disease state.
Bibliographic record
Abstract
6530 Background: In the phase 3 KEYNOTE-048 trial ( NCT02358031 ) in R/M HNSCC (N = 882), 1L P vs E showed superior OS in PD-L1 CPS ≥20 and CPS ≥1 populations, noninferior OS in the total population, no PFS benefit, and favorable safety; 1L P+C vs E showed superior OS in CPS ≥20, CPS ≥1, and total populations, no PFS benefit, and comparable safety. Results of P or P+C vs E in incurable recurrent only, metastatic only, and R/M subgroups are shown. The metastatic only and R/M subgroups were combined and classified as metastatic. Methods: Patients with incurable recurrent (local and/or regional node recurrent disease) or metastatic HNSCC were randomly assigned 1:1:1 to P, P+C, or E. OS and PFS were estimated using the Kaplan-Meier method. Hazard ratios and 95% CIs were based on a Cox regression model with Efron’s method of tie handling with treatment as a covariate stratified by ECOG performance status, HPV status, and PD-L1 status. Data cutoff: Feb 25, 2019. Results: In the incurable recurrent only subgroup (n = 252), median OS was 11.5 vs 12.1 mo (P vs E) and 13.0 vs 11.1 mo (P+C vs E). In the metastatic subgroup (n = 620), median OS was 11.4 vs 9.7 mo (P vs E) and 13.0 vs 10.1 mo (P+C vs E). Median follow-up, OS, and PFS are shown in Table. Treatment-related adverse events (TRAE) in the incurable recurrent only subgroup: 49.4% (P), 94.7% (P+C), and 97.8% (E); grade 3-5 TRAEs rates: 16.0%, 78.7%, and 73.3%, respectively. TRAE rates in the metastatic subgroup: 61.6% (P), 96.4% (P+C), and 96.4% (E); grade 3-5 TRAEs rates: 17.6%, 69.5%, and 67.0%, respectively. Conclusions: P and P+C vs E were efficacious in the metastatic subgroup; in the relatively smaller subgroup of patients with incurable recurrent only HNSCC, the effect was less pronounced. Consistent with the total study population and regardless of disease state, the safety profile was favorable with P vs E and comparable with P+C vs E. These data further support use of 1L P or P+C in patients with R/M HNSCC. Clinical trial information: NCT02358031 . [Table: see text]
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 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".