Combining radiation with the PD-1 inhibitor pembrolizumab appeared to be safe and effective in patients with stage III-IV head and neck squamous cell carcinoma who are ineligible for cisplatin, according to the results of a phase 2 study.

According to the study, preclinical data has suggested that radiotherapy can increase sensitivity to immunotherapy and that immunotherapy can sensitize cancer cells to radiation.

Therefore, the researchers conducted a single-arm phase 2 study in 29 patients ineligible for standard cisplatin testing radiotherapy concurrently with 3 cycles of pembrolizumab followed by three adjuvant cycles. The primary endpoint was progression-free survival at 16 months or longer.

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With a median follow-up of just under 2 years, the estimated 24-month progression-free survival was 71% and the 24-month overall survival was estimated to be 75%. The median progression-free survival was not reached, meeting the primary endpoint of progression-free survival of at least 16 months. Patients’ PD-L1 expression did not predict for progression.

According to the researchers, the toxicities observed were typical of radiotherapy. However, high rates of grade 3/4 lymphopenia (58.6%) were observed.

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“Given that the mechanism of action of pembrolizumab is checkpoint inhibition of T cells, this toxicity is relevant to efficacy, safety, and future directions,” the researchers wrote.

To evaluate it further, they characterized the lymphopenia using flow cytometry. They  observed an increase in frequencies of transitional B cells and tissue-like memory C cells; rates of memory B cells decreased. Those patients who progressed had greater percentages of baseline naive B cells and fewer marginal zone B cells.

According to the researchers, multiple clinical studies to further evaluate immunoradiotherapy in head and neck cancer are underway.


Weiss J, Sheth S, Deal AM, et al. Concurrent definitive immunoradiotherapy for patients with stage III-IV head and neck cancer and cisplatin contraindication [published online May 5, 2020]. Clin Cancer Research. doi: 10.1158/1078-0432.CCR-20-0230