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UNC Lineberger’s Jared Weiss, MD, presented preliminary findings at the 2020 Multidisciplinary Head and Neck Cancers Symposium from a phase II trial that combined radiation therapy and immunotherapy for patients with locally advanced head and neck squamous cell carcinoma.

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UNC Lineberger’s Jared Weiss, MD.

The study evaluated a combination of radiation and pembrolizumab —an immunotherapy drug known as a “checkpoint inhibitor.” According to a release on the preliminary study from the American Society for Radiation Oncology, researchers believe the combination could offer a new treatment option for patients who are ineligible for cisplatin chemotherapy, part of standard treatment for the disease.

“That is a common dilemma in the exam room because cisplatin, while effective, tends to be particularly toxic for patients and can lead to permanent side effects for some,” said Weiss, who is a UNC Lineberger member and associate professor of medicine at the UNC School of Medicine Division of Hematology/Oncology. “I will have patients I want to treat with platinum chemotherapy, but I also want to align treatment with their values. Is the patient willing to accept a risk of deafness or exacerbated ringing in their ears? These are not acceptable consequences for most people.”

About the clinical trial

The single-arm trial included 29 patients with locally advanced head and neck squamous cell carcinoma. It was designed specifically for patients with locally advanced disease who normally would receive platinum chemotherapy together with radiation, but may not be able to tolerate its side effects.

The side effects could occur due to preexisting hearing problems that place patients at risk of permanent hearing loss.

Preexisting kidney and nerve damage also tend to be aggravated by cisplatin and place patients at risk for permanent side effects.

Patients were treated with three cycles of pembrolizumab and concurrent radiation therapy over six weeks, followed by three additional cycles of the immunotherapy drug.

Preliminary findings

With a median follow-up of 21 months, the rates of one-year progression-free and overall survival were 76 percent [95% CI 56-88] and 86 percent [67-95], respectively.

Researchers reported that toxicities were mild with the exception of grade 3-4 lymphopenia, which affected 59 percent of patients.

“This toxicity profile is better than what patients generally experience with cisplatin and radiation,” Weiss said. “It was more consistent with what we see from radiation therapy alone, with the exception of a high rate of lymphopenia that warrants additional study.”

While using the PD-1/PD-L1 blockade following chemoradiotherapy has improved survival in lung cancer, this trial is one of the first to show its potential efficacy for head and neck cancers.

“There are convincing arguments that radiation sensitizes patients to immunotherapy and can enhance its effects,” Weiss said. “And the opposite direction also seems to be true – radiation therapy needs a functional immune system to work, and our hope was that pembrolizumab might be a radiation sensitizer for these patients.”

Weiss cautioned that findings need confirmation in a randomized trial before the combination is recommended to patients.

He presented the abstract, “Progression-free survival, overall survival and immunophenotyping outcomes for patients with stage III-IV head and neck cancer and cisplatin contraindication treated with definitive radiotherapy plus pembrolizumab” during Oral Abstract Session of the symposium, which was held Feb. 27-29 in Scottsdale, Arizona. The study was funded by Merck.