Recent Failures Spur Innovation in Head and Neck Cancer Trials

After unfavorable results from the phase 3 KEYNOTE-412 (NCT03040999) and JAVELIN Head and Neck 100 (NCT02952586) trials in head and neck cancers, researchers analyzed the results to develop their next moves. To enhance outcomes emerging new trial designs are already showing improvement.^1,2

In this video, Trisha Wise-Draper, MD, PhD, professor of medicine in the Division of Hematology/Oncology and section head of medical oncology at UC Health, Ohio, provides an overview of the advancements for the management of head and neck cancers.

“There were a lot of questions about those studies and why they might have failed. Some [surmise] that it may have been just the timing,” Wise -Draper explains regarding the KEYNOTE-412 and JAVELIN Head and Neck 100 studies. “There have been subsequent studies, at least in the adjuvant setting, that sequence the pembrolizumab or PD-1 inhibitor after the radiation, instead of concurrently. This may be a better sequential way of doing it to enhance the immune response, rather than doing concurrent treatment.”

She explains that phase 2 trials, one conducted by herself and one by Ravindra Uppaluri, MD, PhD, director of Head and Neck Surgical Oncology at the Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, explored treatment in the neoadjuvant setting.^3,4 In these trials, investigators evaluated neoadjuvant immunotherapy as a monotherapy followed by immunotherapy plus radiation and chemotherapy or radiation alone. These landmark trials await being presented at upcoming conferences.

Next steps include separating neoadjuvant and adjuvant approaches to better understand their benefit and understand the importance of pathological response for this cancer type, Wise-Draper explains.

REFERENCES

1. Lee NY, Ferris RL, Psyrri A, et al. Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial. Lancet Oncol. 2021;22(4):450-462. doi:10.1016/S1470-2045(20)30737-3

2. Machiels JP, Tao Y, Licitra L, et al. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial. Lancet Oncol. 2024;25(5):572-587. doi:10.1016/S1470-2045(24)00100-1

3. Wise-Draper TM, Gulati S, Palackdharry S, et al. Phase II clinical trial of neoadjuvant and adjuvant pembrolizumab in resectable local-regionally advanced head and neck squamous cell carcinoma. Clin Cancer Res. 2022;28(7):1345-1352. doi:10.1158/1078-0432.CCR-21-3351

4. Uppaluri R, Campbell KM, Egloff AM, et al. Neoadjuvant and adjuvant pembrolizumab in resectable locally advanced, human papillomavirus-unrelated head and neck cancer: a multicenter, phase II trial. Clin Cancer Res. 2020;26(19):5140-5152. doi:10.1158/1078-0432.CCR-20-1695