Nivolumab Reduces Transformation of Precancerous Leukoplakia to Oral Cancer

Glenn J. Hanna, MD, director of the Center for Salivary and Rare Head and Neck Cancers, physician at Dana-Farber Cancer Institute, and assistant professor of medicine at Harvard Medical School, discusses the results of a study investigating nivolumab (Opdivo) as treatment for proliferative leukoplakia (PL) leading to oral cancer.

PL is an aggressive precancerous condition that can transform into oral squamous cell carcinoma. The single-arm phase 2 study (NCT03692325) enrolled 33 patients with PL to receive nivolumab every 28 days for up to 4 cycles. The investigators reported a decrease in composite score based on size and degree of dysplasia of at least 40% in 36% of patients. Hanna says that PL lesions are unlikely to regress without treatment.

The investigators also observed continued improvement several months after patients had received their last dose of nivolumab, which is consistent with nivolumab’s use in cancer treatment. This shows it may take longer to be effective, and longer-term treatment may improve outcomes further, according to Hanna.

There was a 78% rate of cancer-free survival at 2 years, which is encouraging given the high risk of PL transforming into cancer. Hanna says they intend to follow patients to see 5-year cancer-free survival as well. The study shows that immunotherapy can play a role in preventing cancer in patients with precancerous oral disease.

TRANSCRIPTION:

0:08 | We saw a 36% regression rate or response rate. So this means that upwards of 36% of patients had more than 40% regression in their lesion sizes and/or the degree of dysplasia in those lesions; remember [they had] up to 1 to 3 lesions [biopsied]. So that was exciting to see. Importantly, we would not expect PL lesions to regress spontaneously. Some people would say, “Could that just be the ebbs and flows of the disease?” No, we don't expect these lesions to get better. These are so high risk that they would likely evolve over time into cancer.

0:50 | The other thing we noticed was that there were some patients who had clinically visible regression, and we showed clinical photographs in our slides at ESMO [2022 European Society of Medical Oncology Annual Congress], showing that some lesions regressed and that even carried on well beyond exposure to nivolumab. So even after the 4 doses, months and months later, which we can observe in advanced cancer patients with immunotherapy, we saw some improvements in clinical leukoplakia. That means this may take a while to work, and so the question of whether we should be giving more doses comes up.

1:29 | I think the other thing was the 2-year cancer free survival. It's a short interval. But...many of these patients will develop cancer events. It was approaching 78%. That's pretty strong compared [with] our historical data. We certainly will follow these patients out to the median 5-year mark, but at least for a 2-year time point, it's encouraging that almost 80% of patients have not suffered a cancer event.