In-Field Toxicity Analysis of a Phase 1 Clinical Trial of Nivolumab and Ipilimumab With Definitive Radiation Therapy in Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Abstract

Combined modality therapy for locally advanced squamous cell carcinoma of the head and neck (LA SCCHN) is associated with increased toxicities. Immunotherapy has a documented benefit in the recurrent/metastatic setting with a favorable toxicity profile. We evaluated in-field toxicities in the context of a single-institution clinical trial with combined nivolumab, a PD-1 inhibitor, and ipilimumab, a CTLA-4 inhibitor, and concurrent radiation therapy (RT) in patients with LA SCCHN. We analyzed in-field toxicity events in 24 cisplatin-eligible patients with newly-diagnosed LA SCCHN (14 HPV-positive oropharyngeal) treated with nivolumab (3 mg/kg every two weeks for 17 doses) and ipilimumab (1 mg/kg every six weeks for 6 doses) starting two weeks prior to intensity-modulated radiation therapy (IMRT; 70 Gy in 2 Gy fractions). All patients completed RT with no treatment delays. 16/24 patients experienced at least one grade 3 in-field toxicity during radiation treatment including radiation dermatitis (5), dysphagia (6), oral mucositis (10), odynophagia (3), oropharyngeal pain (1), and hoarseness (1). There were no grade 4 or 5 AEs during ICI-RT. Five patients (22%) developed soft tissue ulcers (STU) at the primary tumor site during the consolidation phase, one of which led to a fatal carotid rupture. STUs developed at a median of 91 (range 50-107) days post RT and were negative for viable tumor. Three-year locoregional control rate was 94.7% (95% CI, 85.2%-100%). Concurrent radioimmunotherapy with nivolumab and ipilimumab resulted in excellent locoregional control, but may have an increased the risk of STU. Patients treated with such an approach should be closely monitored for in-field toxicity events, including soft tissue ulceration.