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

by Jennifer L.W. Fink •

Ultimately, it is hoped that checkpoint inhibitors will improve the overall survival rate for head and neck cancers. “What everyone is most excited about is trying to move these agents rapidly into the clinic for treatment of newly diagnosed head and neck cancer,” Dr. Gillison said. “We’re hopeful that the survival benefit we’re seeing in the recurrent metastatic platinum-refractory setting may translate into more cures in the primary setting.”

Jennifer L.W. Fink is a freelance medical writer based in Wisconsin.

Key Points

  • Immunotherapy can now be considered the fourth modality of head and neck cancer treatment.
  • Checkpoint inhibitors ‘unmask’ cancer cells so that the immune system can attack and destroy them.
  • Checkpoint inhibitors are generally well tolerated. In fact, many patients experience fewer adverse events than they did on standard chemotherapy.
  • Head and neck cancers are particularly good targets for checkpoint inhibitors because many are caused by smoking, and the tumors have a high mutational load.
  • 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.

Checkpoint Inhibitors and Radiation

Does radiation therapy enhance the effectiveness of checkpoint inhibitors, or does it increase the likelihood of immune-related toxicities?

So far, preclinical data suggest that checkpoint inhibitors can enhance the local treatment effect of radiation, said Dr. Brizel. Evidence also suggests that checkpoint inhibitors may have abscopal effects, he added. In other words, radiation therapy potentiates the checkpoint inhibitors so that tumors in non-irradiated locations regress after irradiation of one area.

Ongoing and upcoming clinical trials, including NCT02843165 and RTOG3504, are investigating the effects of combining radiation therapy and checkpoint inhibition, or chemotherapy and checkpoint inhibition.

“Right now,” Dr. Brizel said, “we don’t know what the right sequencing is.”—JF

Ongoing and Upcoming Clinical Trials in Immunotherapy for Head and Neck Cancers

Pembrolizumab Plus Docetaxel for the Treatment of Recurrent or Metastatic Head and Neck Cancer (Medical University of Vienna, Austria): The aim of this study combination of docetaxel and pembrolizumab after platinum failure is an effective and safe regimen.

Selection Pressure and Evolution Induced by Immune Checkpoint Inhibitors and Other Immunologic Therapies (University Health Network, Toronto): This study will investigate the feasibility of performing ultra-deep sequencing of ctDNA in patients being treated with checkpoint inhibitors, as well as the clonal evolution of tumors in such patients.