Multicenter phase 2 trial of stereotactic body radiation therapy plus pembrolizumab in PD-1 inhibitor refractory R/M HNSCC

A multicenter phase 2 trial in the United States evaluated stereotactic body radiation therapy (SBRT) combined with pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who progressed on prior PD-1 inhibitor therapy. Eighteen patients were treated: 6 in cohort A in which a single lesion was treated with SBRT while other lesions were left unirradiated, and 12 in cohort B in which all known oligometastatic lesions were treated with SBRT. Pembrolizumab was administered every 3 weeks in both cohorts. The primary endpoint was 3-months progression-free survival (PFS) rate. Median PFS was 1.8 months in cohort A and 5.7 months in cohort B. The 3-months PFS rate was 17% (1/6) in cohort A and 67% (8/12) in cohort B, with no objective responses in cohort A and 3 objective response in cohort B (ORR 25%). Median overall survival was 7.6 months (95% CI 0.7-32.9) in cohort A and 10.1 months (5.8-49.7) in cohort B. In cohort B, 2 (17%) grade 4 toxicities in the setting of re-irrediation were observed. The authors conclude that in anti PD-1-refractory R/M HNSCC, SBRT with pembrolizumab was safe and feasible, suggesting activity when all progressing lesions were treated. These findings support further study and clinical use of comprehensive SBRT plus PD-1 blockade in this hard-to-treat population.