Background: Recurrent head and neck squamous cell carcinomas (HNSCC) in previously irradiated areas are a clinical challenge. Although palliative systemic treatment is a treatment option, the prognosis for many patients remains poor. Reirradiation offers benefit to some patients, but novel approaches are needed to improve durable responses.
Methods: This phase I/II trial evaluated the PD-1 inhibitor nivolumab combined with hyperfractionated reirradiation in patients with recurrent and/or second primary HNSCC ineligible for surgery. Reirradiation target dose was 60 Gy in 40 fractions, 10 fractions per week. Nivolumab was administered biweekly, starting two weeks prior to radiotherapy, for up to 12 months or until progression. Primary objectives were safety and determination of a tolerable nivolumab dose combined with reirradiation.
Results: Twenty patients (55 % male; median age of 72) were enrolled, most with recurrent oral cavity carcinoma. Thirteen participants (65 %) received a reirradiation dose of 60 Gy. All had a PD-L1 combined positive score > 1. Nivolumab dose-escalation reached 3.0 mg/kg biweekly without dose-limiting toxicity. Objective responses (complete and partial) occurred in 40 %, with a mean duration of 8 months. At 12 months the progression free survival (PFS) was 15 %. Median PFS was 6 months and medial overall survival 11 was months.
Conclusion: Combining hyperfractionated reirradiation with a PD-1 inhibitor appears feasible and safe for recurrent HNSCC.
Keywords: Head and neck cancer; Immune checkpoint inhibitors; Immunotherapy; Recurrence; Reirradiation.
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