Abstract LB-258: Efficacy of first-line (1L) pembrolizumab by PD-L1 combined positive score <1, 1-19, and ≥20 in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): KEYNOTE-048 subgroup analysis
Bibliographic record
Abstract
Abstract Introduction: In the phase 3 KEYNOTE-048 trial (NCT02358031) in R/M HNSCC, first-line pembrolizumab (P) monotherapy vs EXTREME (E; chemotherapy [C] + cetuximab) improved overall survival (OS) in PD-L1 combined positive score (CPS) ≥20 and CPS ≥1 populations and led to noninferior OS in the total population with favorable safety; first-line P+C vs E had superior OS in CPS ≥20, CPS ≥1, and total populations with comparable safety. Outcomes in CPS <1 and CPS 1-19 subgroups were not prospectively defined end points; we present a post hoc analysis in these subgroups. Methods: Patients with R/M HNSCC and no prior systemic therapy for R/M disease were randomly assigned 1:1:1 to P, P+C, or E. Progression-free survival (PFS), objective response rate (ORR), and duration of response were assessed by RECIST v1.1 per blinded independent central review. OS and PFS were estimated by 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. Data cutoff was Feb 25, 2019. Results: Baseline characteristics of the CPS <1, CPS 1-19, and CPS ≥20 subgroups were similar to those of the total population. In the CPS <1 subgroup, the HR (95% CI) for OS was 1.51 (0.96-2.37) for P (n = 44) vs E (n = 45) and 1.21 (0.76-1.94) for P+C (n = 39) vs E (n = 43) (Table). In the CPS 1-19 subgroup, HR (95% CI) for OS showed a slight advantage of P (n = 124) vs E (n =133) (0.86 [0.66-1.12]) and favored P+C (n = 116) vs E (n = 125) (0.71 [0.54-0.94]). Conclusions: There was overall evidence of increased efficacy with increasing PD-L1 expression. In the CPS 1-19 subgroup, P+C vs E results were consistent with treatment benefit. Analysis of the CPS <1 subgroup was limited by small patient numbers. Future exploratory analyses of tumor mutational burden and inflamed signatures could further evaluate predictors of benefit in patients with low PD-L1-expressing HNSCC. Table.Efficacy in subgroups of patients with PD-L1 CPS <1, CPS 1-19, and CPS ≥20CPS subgroupTreatmentMedian OS, moOS HR12-mo OS rate, %Median PFS, moPFS HRORR, nMedian DOR, mo(95% CI)(95% CI)(95% CI)(95% CI)(95% CI)(%)(range)<1Pembrolizumab7.91.5138.62.14.3122.6n = 44(4.7-13.6)(0.96-2.37)(24.5-52.6)(1.9-2.3)(2.63-7.08)(4.5)(2.2-3.0)<1EXTREME11.3_48.96.2_197.8n = 45(9.1-15.9)(33.7-62.4)(5.1-7.6)(42.2)(2.0-38.6+)<1Pembrolizumab + Chemotherapy11.31.2141.04.71.46125.7n = 39(9.5-14.0)(0.76-1.94)(25.7-55.8)(3.4-6.2)(0.93-2.30)(30.8)(2.6-20.6+)<1EXTREME10.7_46.56.2_174.3n = 43(8.5-15.9)(31.2-60.4)(5.0-7.3)(39.5)(2.0-31.2+)1-19Pembrolizumab10.80.8644.02.21.2518NRn = 124(9.0-12.6)(0.66-1.12)(35.1-52.5)(2.1-2.9)(0.96-1.61)(14.5)(1.5+-38.9+)1-19EXTREME10.1_42.44.9_455.0n = 133(8.7-12.1)(33.9-50.7)(3.8-6.0)(33.8)(1.4+-38.7+)1-19Pembrolizumab + Chemotherapy12.70.7152.64.90.93345.6n = 116(9.4-15.3)(0.54-0.94)(43.1-61.2)(4.2-5.3)(0.71-1.21)(29.3)(1.6+-25.6+)1-19EXTREME9.9_41.14.9_424.6n = 125(8.6-11.5)(32.4-49.6)(3.7-6.0)(33.6)(1.4+-31.4+)≥20Pembrolizumab14.80.5856.43.40.993122.6n = 133(11.5-20.6)(0.44-0.78)(47.5-64.3)(3.2-3.8)(0.76-1.29)(23.3)(2.7-43.0+)≥20EXTREME10.7_44.95.3_444.2n = 122(8.8-12.8)(35.9-53.4)(4.8-6.3)(36.1)(1.2+-31.5+)≥20Pembrolizumab + Chemotherapy14.70.6057.15.80.76547.1n = 126(10.3-19.3)(0.45-0.82)(48.0-65.2)(4.7-7.6)(0.58-1.01)(42.9)(2.1+-39.0+)≥20EXTREME11.0_46.15.3_424.2n = 110(9.2-13.0)(36.6-55.1)(4.9-6.3)(38.2)(1.2+-31.5+) Citation Format: Barbara Burtness, Danny Rischin, Richard Greil, Denis Soulières, Makoto Tahara, Gilberto de Castro, Amanda Psyrri, Neus Basté, Prakash Neupane, Åse Bratland, Thorsten Fuereder, Brett G. Hughes, Ricard Mesia, Nuttapong Ngamphaiboon, Tamara Rordorf, Wan Zamaniah Wan Ishak, Joy Ge, Ramona Swaby, Burak Gumuscu, Kevin Harrington. Efficacy of first-line (1L) pembrolizumab by PD-L1 combined positive score <1, 1-19, and ≥20 in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): KEYNOTE-048 subgroup analysis [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-258.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.006 |
| Bibliometrics | 0.001 | 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) | 0.006 | 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".