Single-center phase 2 trial of pembrolizumab plus quad-shot radiotherapy for recurrent, unresectable, or metastatic HNSCC

Immune checkpoint inhibitor monotherapy for patients with recurrent, unresectable, or metastastatic head and neck squamous cell carcinoma (RUM HNSCC). Low-dose, hypofractionated, quad shot radiotherapy (QSRT) may enhance the effect of ICIs. A phase 2 trial at Wake Forest University School of Medicine (Winston-Salem, NC) evaluated ICIs in combination with QSRT in patients with RUM HNSCC. Pembrolizumab 200 mg/m² was administered every three weeks until disease progression, intolerance, or a maximum duration or 2 years. QSRT comprised 14.8 Gy in four 3.7-Gy fractions that were delivered twice daily on consecutive days. QSRT courses were delivered cyclically between pembrolizumab cycles. The primary outcome was overall response rate (ORR). Of the 29 individuals who were screened, 21 enrolled, and 15 patients were eligible for response analysis. Fourteen patients had received prior systemic therapy, and 11 had received prior RT. Among evaluable patients, the ORR was 47% (95% CI 21-73). Median progression-free survival and overall survival among 20 treated patients were 9.2 months (95% CI 3-17) and 14.9 months (5-NE), respectively. Among the 15 patients evaluable for the primary endpoint, median PFS was 11.5 months (95% CI 5.1-NE) and median OS was 15.3 months (6.3-NE). Grade 3 and 4 adverse events occurred in 6 and 2 patients, respectively. The authors conclude that pembrolizumab plus QSRT for patients with RUM HNSCC was feasible and showed preliminary evidence of a potential benefit.