A striking 63.3% of patients with stage II–IV cutaneous squamous cell carcinoma (CSCC) saw their tumors nearly or completely disappear when treated with immunotherapy before surgery, according to an international, multicenter, Phase II clinical trial led by The University of Texas MD Anderson Cancer Center. The results were presented today at the European Society for Medical Oncology (ESMO) Congress 2022 and published in The New England Journal of Medicine.

The anti-PD1 therapy cemiplimab was well-tolerated, and the study met its primary endpoint with a pathologic complete response (pCR) rate of 50.6. Another 12.7% of patients had a major pathological response (MPR), with less than 10% viable tumor found at surgery.

“These results represent the highest response rate to neoadjuvant anti-PD1 monotherapy in any solid cancer so far and likely are the start of a practice change for how we treat advanced, resectable cutaneous squamous cell carcinoma,” said study principal investigator and lead author Neil Gross, MD, professor of Head and Neck Surgery at MD Anderson. “I’m excited to see how this new treatment approach impacts outcomes, including quality of life, as we continue long-term follow-up.”

About one million people in the U.S. are diagnosed with CSCC each year, making it one of the most common forms of cancer. Most cases are easily treated by a dermatologist or primary care physician and do not require advanced care. However, most CSCCs occur in the head and neck regions—areas that receive heavy sun exposure—and, in the rare instances that they do grow and spread aggressively, they can affect the eyes, ears, nose and mouth.

The current standard of care, involving surgical excision and radiation, can be disfiguring and result in loss of important functions. Although not an endpoint of the study, the response to neoadjuvant (pre-surgical) immunotherapy enabled less invasive, function-preserving surgery in some cases.

In 2018, the Food and Drug Administration (FDA) approved cemiplimab for patients with metastatic CSCC who are not candidates for curative surgery or radiation. The drug was first studied in a single-institution phase II study at MD Anderson. The results were presented at the ESMO Congress 2019 and published in Clinical Cancer Research in 2021. The 75% pathologic response rate from 20 patients in that study prompted this larger, international, multicenter study (NCT04154943) to confirm the drug’s efficacy.

This single-arm study enrolled 79 patients in the U.S., Australia and Europe with operable stage II–IV CSCC to receive four doses of neoadjuvant cemiplimab followed by curative-intent surgery, with optional adjuvant radiation therapy. Patients had scans before surgery, but the imaging responses (6.3% complete response) underestimated pCR (50.6%). The overall response rate from imaging was 68.4%, with most responses classified as partial responses.

Sixty-seven patients (84.8%) were male and the median age was 73. Consistent with CSCC incidence, 87.3% of patients were white, and the head and neck region was the primary cancer site for 91.9% of patients.

Sixty-two patients received all four doses and 70 patients underwent surgery. Of the nine patients who did not have surgery, three declined because imaging showed their cancer responded to the immunotherapy, two were lost to follow-up/non-compliance, two had progressive disease and two experienced adverse events.

“I think where it’s really going to make a huge difference is quality of life,” Gross said. “If you can avoid radiation or have a smaller surgery, and you can keep your eye, ear or nose, that’s a huge win for people. That’s the excitement of this approach: the chance to make life so much better for our patients in the future.”

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