Safety Evaluation of Nivolumab Concomitant With Platinum-Based Chemoradiation therapy for Intermediate and High-Risk Local-Regionally Advanced Head and Neck Squamous Cell Carcinoma: RTOG Foundation 3504

Abstract

Nivolumab (Nivo), which inhibits the programmed death-1 (PD-1) receptor, improved survival for patients (pts) with platinum-refractory recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) compared with standard therapy. A clinical trial was designed to evaluate the safety of adding nivo to four standard radiation therapy (RT) regimens for pts with newly diagnosed intermediate (IR) and high-risk (HR) HNSCC (Table 1). Early safety data for cohort 1 (weekly cisplatin) and accrual for cohort 2 (high-dose cisplatin) are reported. Eligibility includes IR (p16+, oropharynx T1-2N2b-N3/T3-4N0-3, >10 pack-years (pys) or T4N0-N3, T1-3N3 ≤10 pys) and HR HNSCC (oral cavity, larynx, hypopharynx, or p16(-) oropharynx, stage T1-2N2a-N3 or T3-4N0-3). Ten pts are enrolled to obtain 8 evaluable pts in each cohort. The feasibility of adjuvant nivo at 3-12 months post-RT is also evaluated. Primary endpoints are safety and feasibility, with dose-limiting toxicity (DLT) defined as nivo-related: ≥grade 3 adverse event unresolved to ≤grade 1 in ≤28 days; RT delay >2 wks; incomplete RT; or inability to receive ≥70% of prescribed systemic therapy due to nivo-related toxicity. DLT window was from first nivo dose (day -14) to 28 days post RT. Characteristics of 10 enrolled pts for cohort 1(weekly cisplatin): median age 56, 80% male, 90% caucasian, 40% PS 0, 80% >10 pys, 50% larynx and 50% p16(+) oropharynx cancer, 80% T3-4 and 80% N2-3 disease. Two of 10 pts were unevaluable due to withdrawal of consent. All 8 evaluable pts completed RT. 3 of 8 pts received 10 doses of concurrent nivo: 1 pt received 9 doses, 3 pts are ongoing after 8 doses, and nivo was discontinued due to blurred vision in 1 pt after 8 doses. Seven of 8 pts received >70% of prescribed cisplatin, which was discontinued early in 3 pts due to AEs unrelated to nivo. No DLT was observed. SAEs included anaphylaxis to cisplatin (cis) (n=1), cholecystitis (1), but none attributable to nivo. Grade ≥3 toxicities attributable to nivo included fatigue (n=1), anorexia (1), WBC decrease (2), neutrophil count decrease (1), mucositis (1), lipase (1) elevation. Seven of 8 pts continued on to maintenance nivo. Toxicity data for cohort 2 (high-dose cisplatin), 10 patients accrued, will also be available at the time of the meeting. Nivo is safe and feasible to administer concurrently with a weekly cisplatin-RT regimen for patients with newly diagnosed IR/HR HNSCC (NCT02764593).