Low-Dose Nivolumab with Induction Chemotherapy Improves Responses and Conversion to Radical Therapy in Locally Advanced/Unresectable HNSCC: An Ambispective Real-world Study

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) in patients with 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 biweekly). The median nivolumab dose was 0.51 mg/kg 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 tumors 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/rCR (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 findings of encouraging conversion rate to radical treatment, 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.