The Role of Checkpoint Inhibitors in the Treatment of Head and Neck Cancer

Indeed, immunotherapy can now be considered the fourth modality of head and neck cancer treatment, Dr. Brizel said. “The traditional platform for treating head and neck has been a table with three legs, surgery, radiotherapy, and chemotherapy. Immunotherapy, in essence, brings a fourth leg to the table.”

Monitoring Patients on Checkpoint Inhibitors

Checkpoint inhibitors are generally well tolerated. In fact, many patients experience fewer adverse events than they did on standard chemotherapy. The most common side effects include fatigue, mild diarrhea, and skin rash or itching.

More serious side effects include pneumonitis, colitis, and endocrine system dysfunction. “About 9% of patients experience immune-mediated toxicity,” Dr. Gillison said. “Those are the ones that can be particularly life-threatening, particularly pneumonitis and colitis.”

Red flag symptoms include difficulty breathing, hypoxia, cough (with no obvious cause), and an increase of four or more bowel movements per day above the patient’s baseline. If these symptoms occur in a patient on checkpoint inhibitors, immediate attention is needed. “If symptoms are severe enough to be life-threatening, you may have to stop the therapy permanently. Other times, you can hold it and see if symptoms improve. You may also need to give steroids to suppress the immune system and treat the side effect,” said Pavlos Msaouel, MD, PhD, oncology fellow at MD Anderson and co-author (with Dr. Massarelli) of a 2016 article (Cancer J. 2016;22:108-116).

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. There have been studies showing that the higher the number of mutations in the tumor, the more robust the response to checkpoint inhibitors. —Maura Gillison, MD, PhD

Thyroid dysfunction occurs in approximately 16% of patients, said Dr. Msaouel, so patient thyroid function levels should be monitored during treatment; supplemental thyroid hormone should be given as necessary. Because checkpoint inhibitors can affect the liver as well, liver function tests should be checked. Be alert for hypophysitis; very rarely, the pituitary gland is affected.

Most patients, though, tolerate the medication extremely well. In fact, in the CheckMate-141 study, the patients treated with nivolumab experienced a better quality of life than patients treated with the chemotherapy regimen. They “had sustained physical, emotional, and social functioning, whereas the patients treated with chemotherapy had significant declines,” Dr. Gillison said. “So not only did we see an improvement in survival, but we saw a 60% reduction in moderate to severe toxicity and market stability in quality of life outcomes.”

The Future

Ongoing and upcoming clinical trials hope to answer many unanswered questions, such as when to begin and stop checkpoint inhibition and how to best combine checkpoint inhibitors with chemotherapy, radiation, and other immune-oncology agents. New checkpoint inhibitors are being studied, and researchers are working to better understand the physiology of head and neck tumors, hoping to identify a biomarker that can help physicians determine which patients are likely to benefit from checkpoint inhibition.