Perineural Invasion and Survival in Pembrolizumab‐Treated Head and Neck Squamous Cell Carcinoma

ABSTRACT Objective To determine the relationship between perineural invasion and 6‐month progression‐free survival (PFS)/2‐year overall survival (OS) among patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) on pembrolizumab. Methods This study was a retrospective, observational study performed at a tertiary care academic center. Participants included patients with oral cavity, oropharynx, hypopharynx, and laryngeal head and neck squamous cell carcinoma who began pembrolizumab treatment at UCSF between May 2016 and May 2022. The primary outcome was 6‐month progression‐free survival and 6‐month time‐to‐progression (TTP). The secondary outcome was 2‐year overall survival. Disease progression was determined using radiographic criteria, adopted from the Response Evaluation Criteria in Solid Tumors. Results One hundred and thirty‐three patients with HNSCC were included. Immune checkpoint inhibitor (ICI) indication was recurrence/metastasis for all patients. Forty (30%) patients had perineural invasion. On univariate analysis, patients with perineural invasion were more likely to have worse 6‐month PFS ( p = 0.011). After controlling for number of metastatic organs, receipt of concurrent systemic therapy, age, and PDL‐1 status, presence of perineural invasion was associated with worse 6‐month PFS [HR 3.33 (1.32, 8.41), p = 0.011] and 6‐month time to progression (TTP) [HR 2.14 (1.09, 7.38), p = 0.032], but was not significantly associated with 2‐year OS [HR 1.35 (0.57, 3.19), p = 0.498]. Conclusion Presence of perineural invasion is associated with poorer 6‐month progression‐free survival on ICI in patients with HNSCC. Future studies should further explore how perineural invasion may alter response to immunotherapy. Level of Evidence 3