Low-dose nivolumab plus induction chemotherapy for locally advanced or unresectable head and neck cancer is associated with high response rates and conversion to definitive therapy

Locally advanced head and neck squamous cell carcinoma (LAHNSCC) unresectable at presentation has a dismal survival when radical surgery or definitive chemoradiation is not possible. This ambispective cohort study evaluated the addition of low-dose nivolumab to induction chemotherapy (IC) for locally advanced, unresectable or borderline resectable HNSCC. 111 patients with stage III-IVB disease received IC with low-dose nivolumab (< 240 mg or < 3 mg kg^-1 biweekly). The median nivolumab dose was 0.51 mg kg^-1 biweekly, with a median of 3 doses. Overall response rate per RECIST v1.1 was 75.3% among evaluable patients. 31.6% of oral cavity tumours were rendered resectable, with 32% achieving pathological complete response (pCR). In other sites, the conversion rate to radical chemoradiation was 68.8%. One-year progression-free survival and overall survival were 67% and 83%, respectively, with post-induction radical therapy (p < 0.001) and pCR/radiologic complete response (p < 0.01) correlating with significantly longer PFS. Grade ≥ 3 adverse events occurred in 31.5% of patients. The nivolumab cost was reduced by 88.9% relative to standard dosing. These encouraging conversion rates to definitive therapy, highlight the potential of chemoimmunotherapy as induction therapy in this cohort with a very poor prognosis, with broader implications of cost savings where access to immune checkpoint inhibitors is limited.