A new phase II trial has found that the combination of radiation therapy and pembrolizumab led to improved survival outcomes and acceptable toxicity for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). The combination therapy may offer a new treatment option for patients who are ineligible for cisplatin chemotherapy. Findings will be presented by Jared Weiss, MD, of the University of North Carolina Lineberger Comprehensive Center, at the 2020 Multidisciplinary Head and Neck Cancers Symposium (Abstract LBA 1).

Jared Weiss, MD

The single-arm trial was designed specifically for patients who normally would receive platinum chemotherapy together with radiation but may not be able to tolerate its side effects, most often due to preexisting hearing problems that place patients at risk of permanent hearing loss. Preexisting kidney damage and nerve damage also tend to be aggravated by cisplatin and place patients at risk for permanent side effects.

“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,” explained Dr. Weiss. “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.”

Results

The single-arm trial included 29 patients with locally advanced HNSCC. Reasons for cisplatin ineligibility included otopathology (69.0% of patients), nephropathy (20.7%), and neuropathy (6.9%).

Patients were treated with three cycles of pembrolizumab and concurrent radiation therapy over 6 weeks, followed by three additional cycles of pembrolizumab.

With a median follow-up of 21 months, the rates of 1-year progression-free and overall survival were 76% (95% confidence interval [CI] = 56%–88%) and 86% (95% CI = 67%–95%), respectively. The estimated 2-year progression-free survival rate was 71% (95% CI = 49%–84%) and the estimated 2-year overall survival rate was 75% (95% CI = 51%–88%). For patients with p16-positive oropharyngeal cancer, the 1-year progression-free and overall survival rates were 88% and 94%, respectively; for the other patients, the rates were 58% and 75%.

Most toxicities were mild (grade 1–2), with the exception of grade 3–4 lymphopenia, which affected 59% of patients.

“This toxicity profile is better than what patients generally experience with cisplatin and radiation,” explained Dr. Weiss. “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 programmed cell death protein 1 and programmed cell death ligand 1 inhibitors after 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. 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,” said Dr. Weiss.

The study authors concluded, “Concurrent pembrolizumab and radiotherapy has demonstrated promising progression-free survival and overall survival in locally advanced HNSCC, regardless of p16 status or anatomic location, with a favorable toxicity profile, and deserves evaluation in a randomized trial. The observed changes in B-cell markers deserve further study both as potential biomarkers of treatment response and as therapeutic targets.”

Disclosure: For full disclosures of the study authors, visit astro.confex.com.