Concurrent Definitive Immunoradiotherapy for Patients with Stage III-IV Head and Neck Cancer and Cisplatin Contraindication
Jared Weiss, Siddharth Sheth, Allision M Deal, Juneko E Grilley Olson, Samip Patel, Trevor G Hackman, Jeffrey M Blumberg, Thomas J Galloway, Shetal Patel, Adam M Zanation, Colette J Shen, D Neil Hayes, Christopher Hilliard, Ranee Mehra, Karen P McKinnon, Hsing-Hui Wang, Mark Christian Weissler, Jessica R Bauman, Bhishamjit S Chera, Benjamin G Vincent, Jared Weiss, Siddharth Sheth, Allision M Deal, Juneko E Grilley Olson, Samip Patel, Trevor G Hackman, Jeffrey M Blumberg, Thomas J Galloway, Shetal Patel, Adam M Zanation, Colette J Shen, D Neil Hayes, Christopher Hilliard, Ranee Mehra, Karen P McKinnon, Hsing-Hui Wang, Mark Christian Weissler, Jessica R Bauman, Bhishamjit S Chera, Benjamin G Vincent
Abstract
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.
Patients and methods: This single-arm, multi-institution, phase II study (NCT02609503) enrolled 29 cisplatin-ineligible patients. Patients received radiotherapy concurrently with three cycles of pembrolizumab 200 mg every 3 weeks followed by three adjuvant cycles. The primary endpoint was a progression-free survival (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 24-month PFS and overall survival rates were 71% (95% confidence interval, 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.
©2020 American Association for Cancer Research.
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Source: PubMed