Immunotherapy in Head and Neck Squamous Cell Carcinoma With PD-L1 Combined Positive Score Less Than 1: A Bayesian Meta-Analysis
A partir d'une revue de la littérature publiée entre 2018 et 2025 (7 essais, 630 patients), cette méta-analyse évalue l'efficacité, du point de vue de la survie globale, et la toxicité de l'immunothérapie chez les patients atteints d'un carcinome épidermoïde de la tête et du cou n'exprimant pas ou exprimant peu PD-L1 (score CPS inférieur à 1)
Importance : Immune checkpoint inhibitors (ICIs) are recommended for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), including patients with tumors with a programmed cell death 1 ligand 1 (PD-L1) combined positive score (CPS) of less than 1. However, the benefit of ICIs in this population remains uncertain.
Objective : To quantify the probability that ICIs are associated with improved or reduced survival in HNSCC with a PD-L1 CPS of less than 1 compared with standard non-ICI therapy.
Data Sources : Systematic search of PubMed, Embase, Web of Science, and ClinicalTrials.gov from database inception to January 11, 2026.
Study Selection : Phase 3 randomized clinical trials comparing ICI-based regimens vs standard non-ICI control in HNSCC reporting outcomes in the subgroup with a PD-L1 CPS of less than 1.
Data Extraction and Synthesis : The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was followed. Bayesian random-effects meta-analysis estimated hazard ratios (HRs) with 95% credible intervals (CrIs) and the posterior probability of HR being greater than 1.0 (favoring control), a continuous measure of evidence. Frequentist random-effects meta-analysis also estimated HRs with 95% CIs and P values to assess statistical significance. All processes were performed independently by at least 2 reviewers, with discrepancies resolved through discussion or adjudication by a senior investigator.
Main Outcomes and Measures : The primary outcome was overall survival (OS), and the secondary outcome was a composite of disease-free survival (DFS), progression-free survival (PFS), and event-free survival (EFS).
Results : The meta-analysis included 7 randomized clinical trials from 2018 to 2025 involving 630 patients with tumors with a PD-L1 CPS of less than 1. In the recurrent/metastatic setting (3 trials), the bayesian HR for OS was 1.42 (95% CrI, 0.93-2.06), with a posterior probability of an HR exceeding 1.0 of 95.6%. The frequentist HR was 1.46 (95% CI, 1.17-1.83; P < .001). In the locally advanced setting (4 trials), the bayesian HR for the composite of DFS, PFS, and EFS was 1.19 (95% CrI, 0.72-2.06), with posterior probability of an HR exceeding 1.0 of 76.8%. Across all trials, the bayesian HR was 1.43 (95% CrI, 0.97-2.07) for OS (4 trials) and 1.30 (95% CrI, 0.94-1.75) for the composite of DFS, PFS, and EFS (6 trials), with posterior probability of an HR exceeding 1.0 of 96.2% and 95.5%, respectively. The frequentist HRs were 1.47 (95% CI, 1.18-1.83) for OS and 1.31 (95% CI, 1.02-1.69) for the composite of DFS, PFS, and EFS.
Conclusions and Relevance : This systematic review and meta-analysis found a high bayesian probability, alongside frequentist statistical significance, that ICIs were associated with reduced OS in patients with HNSCC with a PD-L1 CPS of less than 1. These subgroup-derived findings warrant validation and cautious use in this understudied population.
JAMA Oncology , résumé, 2026