Neoadjuvant Immunotherapy for Skin Cancer

Advanced squamous cell carcinoma threatened the patient’s eye. Although most cases of cutaneous squamous cell carcinoma can be effectively treated via simple excision, this patient’s cancer was large, disfiguring, and potentially life-altering, as surgical treatment would likely require enucleation.

“The standard of care for patients with locally advanced, resectable head and neck squamous cell carcinomas is surgery and radiation. But given the proximity of the pathology to critical structures, like the eye, ear, lips, and nose, surgery can be functionally devastating,” said Neil D. Gross, MD, professor and director of clinical research in the department of head and neck surgery at MD Anderson Cancer Center in Houston. “Some patients lose an eye, or an ear, or big parts of their scalp.”

Neoadjuvant immunotherapy may allow some patients with locally advanced squamous cell carcinoma to avoid disfiguring and functionally devastating surgeries. In 2017, Dr. Gross launched a small clinical trial testing immunotherapy prior to surgery and found that “with just two doses of the drug before surgery, the tumors started melting away,” he said. “For 11 out of 20 patients, by the time we went to surgery, there was no tumor left; it was completely gone. For another four patients, it was almost completely gone.” (Clin Cancer Res. 2021;27:4557–4565).

Dr. Gross and others have since conducted a phase two, confirmatory, multicenter, nonrandomized study to evaluate cemiplimab, a PD-1/PD-L1 checkpoint inhibitor, as neoadjuvant therapy in patients with resectable stage II, III, or IV cutaneous squamous cell carcinoma of the head and neck. Again, results were positive. “There was nothing left of the cancers in just over half of the patients,” Dr. Gross said. “In another handful of patients, the cancer was almost completely gone.” (N Engl J Med. 2022;387:1557–1568). Some patients were able to keep their eyes (and vision).

Will neoadjuvant immunotherapy eventually become the standard of care for patients with locally advanced, resectable squamous cell carcinoma of the head and neck? Perhaps. Additional questions must be answered first.

Here’s what’s currently known—and not yet known—about neoadjuvant immunotherapy for advanced squamous cell carcinoma.

New Treatment Options for Previously Underserved Patients

Cutaneous squamous cell carcinoma is the second most common form of skin cancer worldwide, and approximately 2% to 5% of patients present with locally advanced cancers (Clin Cancer Res. 2021;27:4557–4565). Treatment is challenging— particularly because many patients are of advanced age and have other comorbid conditions—and may be disfiguring and disabling. Approximately 30% of patients with locoregionally advanced resectable cutaneous squamous cell carcinoma eventually die of the disease, despite treatment (Clin Cancer Res. 2021;27:4557–4565). “These patients have been underserved for a long time,” Dr. Gross said.