Safety of pembrolizumab with chemoradiation (CRT) in locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN).

Abstract

6011 Background: Pembrolizumab (pembro) is a humanized monoclonal antibody that blocks the programmed death receptor-1 (PD-1) interaction with its ligands (PD-L1, PD-L2). While pembro is approved for platinum-refractory, recurrent/metastatic SCCHN, its role in definitive therapy for LA-SCCHN is not yet defined. Here we present the safety results of pembro with cisplatin-based CRT for patients (pts) with LA-SCCHN (NCT02586207). Methods: 27 pts with oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (L) stage III-IVB SCCHN (any HPV status) eligible for cisplatin-based, definitive CRT were enrolled from November 2015 to August 2016 as part of a safety cohort. Pembro was given at a fixed dose of 200 mg IV 4-7 days prior to initiation of CRT and then every 3 weeks during CRT (2 concomitant doses) and then following CRT for 5 additional doses. CRT consisted of weekly cisplatin 40 mg/m2 IV x 6 doses (240 mg/m2 maximum) given concurrently with radiation at a dose of 2 Gy once daily for 35 fractions (total 70 Gy). Safety was determined by the occurrence of CRT or pembro dose-limiting adverse events (AEs) and immune-related AEs (irAEs). Efficacy was defined as complete response (CR) rate on imaging or with salvage surgery at 100 days post-CRT completion. Results: 20 (74%) pts with OP HPV+ and 7 (26%) pts with HPV- (4 L, 2 OP, 1 HP) tumors were enrolled. 21 (78%) completed all planned doses of pembro. 3 discontinued due to irAEs (G2 peripheral motor neuropathy, G3 AST elevation, G1 Lhermitte-like syndrome). 3 discontinued due to protocol reasons (early neck dissection -2 pts, prolonged hospitalization-1 pt). All pts completed the full radiation dose (70 Gy) without significant delay (defined as > 5 days). 23 (85%) received the goal target dose of cisplatin (≥200 mg/m2). There was one pt death due to concurrent illness, unrelated to treatment. The study has been reopened with expansion cohorts of 34 HPV+ pts and 23 HPV- pts to evaluate efficacy. Conclusions: Pembro in combination with weekly cisplatin-based CRT is safe and does not significantly impair radiation or chemotherapy dosing. Efficacy of this combination is being explored further in this study and through larger phase III clinical trials. Clinical trial information: NCT02586207.