Clinical Outcomes of Pembrolizumab in Head and Neck Squamous Cell Carcinoma Subsites Excluded from the KEYNOTE-048 Trial

TL;DR

This study shows that pembrolizumab is effective and safe for head and neck cancer in areas not tested in a major trial.

Contribution

First evidence of pembrolizumab's efficacy and safety in head and neck cancer subsites excluded from KEYNOTE-048.

Findings

Median overall survival in excluded subsites was 15.2 months with a 70.6% 1-year survival rate.

Median progression-free survival was 4.9 months with a 21.2% 1-year rate in excluded subsites.

Safety profile showed manageable immune-related adverse events with 25.9% incidence and 3.7% Grade ≥ 3 events.

Abstract

Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) carries a poor prognosis. Although the KEYNOTE-048 trial established the efficacy of pembrolizumab, it was restricted to major sites such as the oral cavity, oropharynx, hypopharynx, and larynx. Subsites including the paranasal sinuses, nasopharynx, external ear, and salivary glands were excluded, and evidence regarding these locations is lacking. In this multicenter retrospective study, we evaluated 167 patients treated with pembrolizumab, including 27 with tumors in excluded subsites. The median overall survival in the excluded subsite group was 15.2 months (1-year rate: 70.6%), and median progression-free survival was 4.9 months (1-year rate: 21.2%). Survival outcomes in this group did not differ significantly from those in included sites. The safety profile was manageable. This study is the first to demonstrate the potential efficacy and safety of pembrolizumab in patients with tumors in subsites excluded from KEYNOTE-048.

Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) carries a poor prognosis; however, immune checkpoint inhibitors have emerged as critical therapeutic options. Although the KEYNOTE-048 trial established the efficacy of pembrolizumab, the population was restricted to major sites (e.g., oral cavity, oropharynx, hypopharynx, and larynx), excluding subsites such as the paranasal sinuses and nasopharynx. To evaluate outcomes in these populations, we conducted a multicenter retrospective study of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022. The cohort comprised 127 patients with tumors in included sites and 27 in excluded subsites. Primary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAEs). In the excluded subsite group, median OS was 15.2 months (1-year rate: 70.6%), and median PFS was 4.9 months (1-year rate: 21.2%). The ORR was 22.2% and the DCR was 59.3%. The incidence of irAEs was 25.9%, with Grade ≥ 3 events in 3.7%. Survival outcomes did not differ significantly from those in included sites. These findings suggest the potential efficacy and safety of pembrolizumab in subsites excluded from KEYNOTE-048, warranting validation in prospective trials.

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