IMMUNOTHERAPY FOR ORAL CANCER

A short course of neoadjuvant immunotherapy used for the treatment of oral cavity cancers leads to impressive tumor responses as measured by multiple metrics and does not delay definitive surgery, a multicenter, phase 2 study indicates.

"With roughly 3 weeks of treatment, we were able to trigger significant tumor regression," said Jonathan Schoenfeld, MD, MPH, Dana-Farber/Brigham and Women's Cancer Center in Boston, Massachusetts, in a statement.

"Our hope is that even a couple of doses of immunotherapy can stimulate an immune response that continues to prevent the cancer from coming back after patients have surgery and other therapy," he added.

The study was presented at the 2020 Multidisciplinary Head and Neck Cancers Symposium in Scottsdale, Arizona.

"Oral cavity cancer is a notoriously difficult cancer with high rates of disease recurrence and death, and the side effects from standard treatment tend to be particularly challenging because the treated area is essential for speaking, swallowing, and breathing," Schoenfeld said.

Two Treatment Groups

Twenty-nine evaluable patients with newly diagnosed squamous cell carcinoma of the oral cavity were randomly assigned to either two cycles of the programmed death-1 (PD-1) inhibitor nivolumab (Opdivo, Bristol-Myers Squibb) given on weeks 1 and 3 or to the CTLA-4 immune checkpoint inhibitor ipilimumab (Yervoy, Bristol-Myers Squibb), given with nivolumab on week 1 only.

Nivolumab was given at a dose of 3 mg/kg while ipilimumab was given at a dose of 1 mg/kg.

The most common primary tumor site was the oral tongue — 58% of patients had clinically node positive disease and 62% had stage IVA disease.

Patients underwent imaging before and after receiving immunotherapy prior to surgery. Surgery was performed 72 hours to 1 week following cycle 2 restaging scans. The median time to surgery was 19 days.

Treatment in both arms was "relatively well tolerated," Schoenfeld noted.

Immune-related toxicities included grade 3 pneumonitis in one patient and grade 3 colitis in one patient, both in patients treated with the combination of nivolumab and ipilimumab. One patient who received nivolumab monotherapy developed new-onset diabetes requiring treatment with insulin.

"Of note, all of these toxicities occurred following surgical resection, so again, there were no delays to the prespecified surgical date," Schoenfeld emphasized.

Perioperative toxicities included pulmonary embolism, postoperative hematoma, several flap failures, and one perioperative stroke resulting in death.

Volumetric responses — defined as any clinical, radiologic, or pathologic shrinkage of the tumor — were seen in 50% of patients treated with single-agent nivolumab and 53% of patients receiving nivolumab + ipilimumab.

Moreover, "we also observed significant pathologic responses in some patients," Schoenfeld said.

For example, investigators observed a complete pathologic response (greater than 90%) in one patient (8%) treated with nivolumab alone and in three patients (20%) receiving both agents.

At a median follow-up of 14 months, 85% of patients were still free of disease progression at 1 year, and 89% of them were still alive.

At baseline, researchers did not identify any differences in PD-L1 expression in tumor cells between groups.

On the other hand, CD4+ T cells correlated with pathologic response.

Interestingly, this association was only seen in patients treated with nivolumab + ipilimumab but not with nivolumab alone.

"We're excited about moving immunotherapy earlier to treat more of these curative patients and, in the future, possibly reduce how aggressive their other treatments need to be," Schoenfeld observed.

The study was funded by Bristol-Myers Squibb. Schoenfeld declares his institution received research funding from Merck, Bristol-Myers Squibb, and Regeneron. He has served as a consultant or on scientific advisory boards and/or has received travel fees from Immunitas, Debiopharm, Bristol-Myers Squibb, Nanobiotix, Tilos, AstraZeneca, LEK, Catenion, and ACI Clinical.

2020 Multidisciplinary Head and Neck Cancers Symposium: Abstract 1. Presented February 27, 2020.