Another Weapon in the Arsenal
In 2014, the National Cancer Institute’s Head and Neck Steering Committee held a clinical trials planning meeting to discuss the possible role of immunotherapy, including checkpoint inhibitors, in the treatment of head and neck cancer. At the time, checkpoint inhibitors had already shown promise in the treatment of melanoma, renal cell carcinoma, non-small cell lung cancer, urothelial bladder cancer, and recurrent or metastatic squamous cell carcinoma of the head and neck. The group planned priority phase II/III trials to help physicians determine the best ways to integrate immunotherapy into practice.
Since then, researchers have learned that head and neck cancers are particularly good targets for checkpoint inhibitors. Why? Many head and neck cancers are caused by smoking, and the tumors have a high mutational load. “There is some data to suggest that tumors that have frequent mutations in them are more likely to generate tumor-specific neoantigens that T-cells can recognize as foreign in attack. And, there have been studies showing that the higher the number of mutations in the tumor, the more robust the response to checkpoint inhibitors,” Dr. Gillison said.
No one yet knows, though, how to tell which patients will be among the 20% or so who respond to checkpoint inhibitor therapy, and which ones will be among the 80% who do not benefit. “We unfortunately do not have a biomarker to tell us for sure if the patient will respond or not,” said Erminia Massarelli, MD, PhD, associate clinical professor of medical oncology at City of Hope in Duarte, Calif. “High mutational load could possibly predict response to immunotherapy, but it’s not ready as a biomarker. The PD-L1 test is a very weak biomarker, because it is a continually changing response; if a tumor is PD-L1 negative, it doesn’t mean that it cannot be PD-L1 positive at some point.”