CSCC Case Raises Questions About Implications of Early Response to Cemiplimab

A patient’s quick response to cemiplimab (Libtayo) was reversed after the therapy was stopped due to progression of apparent metastatic cutaneous squamous cell carcinoma.

Although most patients with cutaneous squamous cell carcinoma (CSCC) can be surgically cured, a new case report highlights the challenges of finding the right therapy for patients with locally advanced or metastatic tumors.

Writing in JAAD Case Reports, the authors outlined the case of a patient with CSCC who had a rapid response to Libtayo (cemiplimab), but later was taken off the therapy and succumbed to his cancer.

The patient, a 61-year-old male, was uninsured and had noticed an enlarging growth on his left cheek for approximately 1 year. When he finally sought care at a volunteer clinic, a biopsy showed he had infiltrating moderately differentiated invasive CSCC. The patient described localized pain, but there was no perineural invasion noted, the authors said. By that time, the tumor was 10 x 8.5 cm in size and was deemed surgically unresectable. A radiation oncologist later said radiation therapy would be ineffective.

Still lacking insurance, it was another 6 months before the patient returned to the clinic, by which point he had lost 20 pounds and the tumor measured 19 x 20 cm, had forced his left eye shut, and apparently affected hearing in his left ear.

There was also more bad news.

“Positron emission tomography-computed tomography revealed an 18F-fluorodeoxyglucose (FDG)-avid mass in the right lung,” the authors said. “There were 3 small (<1 cm) FDG-avid nodular densities in the left lung that were too small for biopsy. A decision was made to monitor closely.”

In the meantime, the patient began receiving cemiplimab, a fully human, hinge-stabilized immunoglobulin G4 monoclonal antibody targeting programmed cell death-1 (PD-1). The drug is approved in both the United States and Europe to treat advanced CSCC.

The patient was given a 350-mg dose at each 3-week treatment cycle. After his very first cycle, the investigators said, his tumor had shrunk by 40% and both his left eye and left ear had improved. By the fifth cycle, the tumor had shrunk to 4 x 6 cm, although the patient was still experiencing weight loss.

Also, in the patient’s lungs, 2 of the 3 nodules had resolved, but one had grown from 6 mm to 2.5 cm. A presumptive diagnosis of metastatic SCC was made, and the patient was discontinued on cemiplimab due to what appeared to be tumor progression. Instead, the patient was put on cetuximab (Erbitux), an epidermal growth factor receptor inhibitor. The therapy helped resolve the lung module, but the facial tumor began to grow again. The patient died 18 months after his initial presentation.

The study investigators the case was notable because of the rapid benefit the patient experienced from cemiplimab. In clinical trials for cemiplimab, the median observed time to response was in the range of 2 months.

“A better understanding of the time to first response and maximum response is critical to evaluate treatment efficacy and may lead to optimization of treatment durations,” the authors wrote, adding that, in non-Hodgkin lymphoma, patients with early responses to anti–PD-1 therapies tended to have better overall outcomes.

The investigators said this case shows why locally advanced CSCC can be difficult to treat. The patient was seeing improvement in the primary tumor on cemiplimab, but fears about the progression of the pulmonary nodule led to a cessation of the therapy and the patient died months later.

“Although the oncologist was focused on the nontarget finding, it is possible that the patient could have been treated by maintaining him on cemiplimab whilst addressing the lung nodule with stereotactic radiation therapy,” the authors wrote.

The investigators said it is not clear why the facial tumor seemed to respond but the pulmonary nodule did not. They said it could be that the primary tumor had a moderately differentiated histology type and the pulmonary nodule had a poorly differentiated type.

“As the decision was made to discontinue cemiplimab, the possibility of pseudoprogression, whereby immune infiltration of tumor leads to the phenomenon of an initial increase in size followed by response in patients treated with [immune checkpoint inhibitors], cannot be excluded,” they wrote.

They concluded that the case shows that more research is warranted to better understand what an early response to cemiplimab means in terms of patient prognosis.

Reference

Zargham H, Strasswimmer J. Rapid response to cemiplimab for advanced cutaneous squamous cell carcinoma. JAAD Case Reports. Published online June 2022. doi:10.1016/j.jdcr.2022.05.031