SCOTTSDALE, AZ-Neoadjuvant immunotherapy for oral cavity cancers can elicit promising responses that could provide long-term benefit for patients, according to a new study.
In a randomized trial, two neoadjuvant doses of the programmed death-1 inhibitor nivolumab given with or without the cytotoxic T-lymphocyte-associated protein 4 inhibitor ipilimumab led to complete or partial tumor shrinkage in more than half of cases and did not delay any patients from continuing on to surgical treatment.
Preclinical and clinical data support neoadjuvant immunotherapy and combinations of immunotherapies, said lead author Jonathan D. Schoenfeld, MD, MPH, Senior Physician at the Dana-Farber/Brigham and Women's Cancer Center and Associate Professor of Radiation Oncology at Harvard Medical School, at the 2020 Multidisciplinary Head and Neck Cancers Symposium. Nivolumab has shown benefit in squamous cell carcinoma (SCC) in the oral cavity, and ipilimumab has demonstrated benefit in the preclinical SCC setting, as well as in clinical treatment of metastatic melanoma.
"We hypothesized that a short 3-week neoadjuvant course of nivolumab with or without ipilimumab would lead to tumor response and not delay definitive surgery in patients with resectable oral cavity cancer," he said. "We were able to trigger significant tumor regression. In a couple cases, there were complete pathological responses, and in other cases, there was very little tumor left. Both the single drug and the two-drug combination led to visible tumor shrinkage and, albeit with relatively early follow-up, the majority of these patients have no evidence of disease recurrence.
"Our hope is that even a couple doses of immunotherapy can stimulate an immune response that continues to prevent the cancer from coming back after patients have surgery and other therapy," Schoenfeld noted.
SCC of the oral cavity historically has poor outcomes, despite standard treatment with surgery followed most often by chemotherapy and radiation. Neoadjuvant immunotherapy may allow the generation of a potential immune response that lasts even after the tumor has been removed and treatment has stopped.
Study Details
The new trial enrolled 30 adults newly diagnosed with tumors in the tongue, gums, or other parts of the mouth (Abstract 1). All tumors were stage T2 or higher, and the majority of tumors were in the tongue, were node-positive, and were stage 4A disease.
After receiving two doses of the nivolumab either alone or in combination with a single dose of ipilimumab over the course of 3 weeks, no patients were delayed from surgery. More than half of the evaluable patients (15 of 29 patients) experienced clinical reduction of their primary tumor after immunotherapy, and four patients (one in the single-drug group, three in the combination group) had more than 90 percent pathologic response.
"With median follow-up of more than 11 months, 90 percent of patients are alive and disease-free," said Schoenfeld.
Immunotherapy was well-tolerated in both arms; however, 21 of the 30 patients experienced side effects possibly related to treatment. These included grade 3-4 toxicities for five patients (33%) in the combination group and two patients (14%) in the single-drug group. By comparison, more than half of patients experienced serious adverse events with the same combination in trials for high-risk resectable melanoma, said Schoenfeld.
These exploratory results are promising, but direct comparisons with the current standard of care are needed to determine whether the single-agent or combination therapy can lead to durable responses and improve patient survival, he said. The researchers also want to understand why immunotherapy worked better with some patients than others and identify additional immune targets that could further enhance the treatment.
Nevertheless, this study adds to a growing body of research on immunotherapy given prior to surgery for patients with newly diagnosed, curable disease. "The preoperative setting is interesting because patients' immune systems haven't been affected by prior treatment. The tumor is actually in place to serve as a focal point for an immune response, so it may be easier for the body's immune system to recognize and target the tumor," explained Schoenfeld.
"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," he continued.
In conclusion, Schoenfeld stated: "Primary endpoints were met with both nivolumab and nivolumab plus ipilimumab, demonstrating promising rates of clinical-pathologic downstaging and pathologic response, including near complete/complete responses.
"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."
Mark L. Fuerst is a contributing writer.