Concurrent definitive immunoradiotherapy for patients with Stage III-IV Head and Neck Cancer and Cisplatin contraindication

Head and Neck Cancer

Weiss J, et al. Clin Cancer Res 2020.


PURPOSE: Although cisplatin plus radiotherapy is a standard treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC), cisplatin contraindication is common. Radiation elicits and promotes tumor-directed immune-stimulation, which may potentiate anti-PD-1 therapy. We provide the first efficacy report of combined pembrolizumab and definitive radiotherapy in LA-HNSCC.

EXPERIMENTAL DESIGN: This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin ineligible patients. Patients received radiotherapy concurrently with 3 cycles of pembrolizumab 200mg q3 weeks followed by 3 adjuvant cycles. The primary endpoint was a PFS of >16 months. Correlative studies included peripheral blood flow cytometry and Luminex cytokine profiling.

RESULTS: Reasons for cisplatin ineligibility included otopathy (69.0%), nephropathy (20.7%), and neuropathy (6.9%). With median follow-up of 21 months, estimated twenty-four month PFS and OS rates were 71% (95% CI 49-84) and 75% (51-88). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. Toxicities were typical of radiotherapy; however high rates of grade 3/4 lymphopenia (58.6%) were observed. Flow cytometry revealed a relative decline in CD4 T cells and B cells, but not CD8 T cells. Upon treatment, frequencies of transitional B cells and tissue-like memory B cells increased while resting memory B cells decreased. Patients with progression had greater percentages of baseline naïve B cells and fewer marginal zone B cells.

CONCLUSIONS: Pembrolizumab and radiotherapy is efficacious in LA-HNSCC and should be evaluated in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers and as therapeutic targets.