In an international, multicenter phase II clinical trial led by the University of Texas MD Anderson Cancer Center, 63.3% of patients with stage II-IV cutaneous squamous cell carcinoma (CSCC) saw their tumors almost or completely disappear when treated with immunotherapy before operation. The results were presented today at the European Society for Medical Oncology (ESMO) Congress 2022 and published in 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%, meaning no tumor cells were found at surgery. An additional 12.7% of patients had a major pathologic response (MPR), with less than 10% viable tumor found at surgery. Responses were confirmed by independent central pathological review.
“These results represent the highest response rate to neoadjuvant anti-PD1 monotherapy in any solid cancer to date and are likely the start of a practice change for how we treat advanced, resectable cutaneous squamous cell carcinoma,” said the study’s principal investigator and lead author Neil. Gross, MD, professor of head and neck surgery. “I am excited to see how this new treatment approach impacts outcomes, including quality of life, as we continue long-term follow-up.”
About 1 million people in the United States are diagnosed with CSCC each year, making it one of the most common types 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 exposed to strong sun—and in the rare cases where they grow and spread aggressively, they can affect the eyes, ears, nose, and mouth.
The current standard of care, which involves surgical excision and radiation, can be disfiguring and result in loss of important functions. Although not a study endpoint, 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 the neoadjuvant setting for operable disease in a single-institution phase II study at MD Anderson, which Gross designed and led. The results were presented at the ESMO Congress 2019 and published in Clinical Cancer Research in 2021. The pathologic response rate of 75% from 20 patients in this study prompted this international multicenter study (NCT04154943) to confirm the drug’s effectiveness.
The single-arm study enrolled 79 patients in the United States, Australia, and Europe with operable stage II-IV CSCC to receive four doses of neoadjuvant cemiplimab followed by curative surgery with optional adjuvant radiation therapy. Patients received scans before surgery, but 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.
67 patients (84.8%) were male, and the median age was 73. Consistent with the incidence of CSCC, 87.3% of patients were white, and the head and neck region was the primary cancer site for 91.9% of patients.
62 patients received all four doses and 70 patients underwent surgery. Of the nine patients who did not undergo surgery, three declined because imaging showed their cancer responded to the immunotherapy, two were lost to follow-up/nonadherence, two had progressive disease, and two experienced side effects.
Overall, 14 patients (17.7%) experienced grade three or higher side effects. The most common events of any grade were fatigue (30.4%), rash (13.9%), diarrhea (13.9%) and nausea (13.9%). Four patients died; one death, a worsening of heart failure, was considered related to treatment. There were no new safety signals for anti-PD1 immunotherapy treatment.
The research team will continue to follow study participants and report survival data and other outcomes once follow-up is complete. In the future, the investigators hope to resolve still unanswered questions about the optimal number of doses before surgery, which patients can safely avoid radiation and/or surgery, and how to predict which patients are most likely to respond to immunotherapy.
“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 minor surgery and you can keep an eye, ear or nose, that’s a huge win for people. That’s the thrill of this approach: the chance to make life so much better for our patients in future.”
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Neoadjuvant cemiplimab for stage II to IV cutaneous squamous cell carcinoma, New England Journal of Medicine (2022). DOI: 10.1056/NEJMoa2209813
Provided by the University of Texas MD Anderson Cancer Center
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