Cemiplimab Approved for Treatment of CSCC

In the past, patients with advanced cutaneous squamous cell carcinoma (CSCC) have had to rely on therapies that are usually ineffective and have not been specifically approved to treat the condition. “Cytotoxic chemotherapy and radiation typically provide only transient palliation at best,” says Paul Nghiem, MD, PhD, of the University of Washington in Seattle. However, with the FDA's recent approval of the PD-1 inhibitor cemiplimab-rwlc (Libtayo; Regeneron), patients with metastatic or locally advanced CSCC who are not candidates for surgery or radiation now have an effective treatment option.

“This medication is life-changing for patients,” says Anna Pavlick, DO, of NYU Langone Health in New York, NY. “Cemiplimab has a response rate near 50%, and many patients will have a long-term, durable response.”

Cemiplimab's approval was based on data from the phase II EMPOWER-CSCC-1 trial and from two phase I expansion cohorts, all open-label. In these trials, which included 108 patients with metastatic or locally advanced CSCC, the overall response rate was 48%, with 61% of responders experiencing a response of 6 months or longer. (Earlier findings from these trials were published in The New England Journal of Medicine in July.)

The FDA relied on these findings because conducting a phase III trial is not practical for advanced CSCC, says Pavlick, who was involved in the EMPOWER-CSCC-1 trial. Although CSCC is the second most common type of skin cancer in the United States, advanced CSCC is uncommon, so recruiting enough participants to conduct a phase III trial would have taken several years. In addition, no standard of care existed for advanced CSCC, which would have made establishing a comparator arm for a phase III trial difficult.

This is the first FDA approval for cemiplimab, which is being tested in a variety of other cancers, including non–small cell lung cancer, multiple myeloma, and cervical cancer.

As for advanced CSCC, Omid Hamid, MD, of The Angeles Clinic & Research Institute in Los Angeles, CA, says he expects this approval to herald a sea change in the way that the condition is treated, similar to the one following the approval of checkpoint inhibitors to treat melanoma and Merkel cell carcinoma.

Other immunotherapies are also being tested for use in advanced CSCC. Trials are under way to investigate both single agents, such as the PD-1 inhibitor pembrolizumab (Keytruda; Merck), and combinations of drugs, such as the PD-1 inhibitor nivolumab (Opdivo; Bristol-Myers Squibb) plus talimogene laherparepvec (Imlygic; Amgen), an oncolytic virus-based drug.

Researchers also want to identify treatments for patients with advanced CSCC who cannot receive immunotherapies. Patients who have had an organ transplant, for example, are much more likely to develop skin cancer than the general population. Unfortunately, they cannot use immune checkpoint inhibitors without risking organ rejection.

For patients with a kidney transplant, “returning to hemodialysis is an option,” says Nghiem. “This puts patients and physicians in a difficult bind: Should they take a chance at prolonged disease control, but lose the precious kidney transplant in the process?” –Kristin Harper