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Weiss J , Sheth S , Deal AM , Grilley Olson JE , Patel S , Hackman TG , Blumberg JM , Galloway T , Patel S , Zanation AM , Shen CJ , Hayes DN , Hilliard C , Mehra R , McKinnon KP , Wang HH , Weissler MC , Bauman JR , Chera BS , Vincent BG
Concurrent definitive immunoradiotherapy for patients with Stage III-IV Head and Neck Cancer and Cisplatin contraindication
Clin Cancer Res. 2020 Aug 15;26(16) :4260-4267
PMID: 32371539    PMCID: PMC7968114    URL: https://www.ncbi.nlm.nih.gov/pubmed/32371539
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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 naive 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.
Weiss, Jared Sheth, Siddharth Deal, Allison M ORCID: https://orcid.org/0000-0003-3526-3938 Grilley Olson, Juneko E ORCID: https://orcid.org/0000-0002-1896-7020 Patel, Samip Hackman, Trevor G Blumberg, Jeffrey M Galloway, Thomas Patel, Shetal Zanation, Adam M Shen, Colette J ORCID: https://orcid.org/0000-0002-3855-7360 Hayes, D Neil ORCID: https://orcid.org/0000-0001-6203-7771 Hilliard, Christopher Mehra, Ranee ORCID: https://orcid.org/0000-0003-2477-9584 McKinnon, Karen P Wang, Hsing-Hui ORCID: https://orcid.org/0000-0003-3283-9583 Weissler, Mark Christian ORCID: https://orcid.org/0000-0002-1709-3763 Bauman, Jessica R Chera, Bhishamjit S Vincent, Benjamin G ORCID: https://orcid.org/0000-0002-1762-2282 Journal Article United States Clin Cancer Res. 2020 May 5. pii: 1078-0432.CCR-20-0230. doi: 10.1158/1078-0432.CCR-20-0230.