Immunotherapy in SCC Still Marred by Challenges, Despite Efficacy in Some Patients

Immunotherapy can have significant clinical benefits for people with squamous cell carcinomas (SCCs) who are not eligible for surgery or radiotherapy, but several hurdles are limiting its usage in the clinic.

In a new review article in International Journal of Molecular Sciences, investigators outlined some of the latest evidence and challenges in using immunotherapy as a treatment for SCC.

They began by outlining data related to the prevalence of melanoma and nonmelanoma skin cancers (NMSCs), which they noted account for 20% to 30% of cancers among White patients in the United States. Melanomas make up just 1% of skin cancer cases in the United States, the authors noted, but they added that melanomas tend to be deadlier than NMSCs.

SCC is the most common NMSC, and it is associated with several risk factors, including exposure to extreme ultraviolet radiation, hereditary predisposition, and immunosuppression, the study authors said.

Once a patient is given a diagnosis of SCC, a number of therapies are potentially available, including surgical excision, radiotherapy, and chemotherapy. However, the authors said not all therapies are an option for all patients.

“In some cases, tumors characterized as advanced, recurrent, located in cosmetically essential areas, or metastatic are not eligible for surgical excision or radiotherapy,” they wrote. “On those occasions, systemic therapies, especially immunotherapies, are the most recommended therapies among other treatments.”

Several factors associated with SCC, including a high tumor mutational burden (TMB), infiltration of immune cells, and the expression of immune checkpoints make the cancer type responsive to immunotherapy, they wrote. The therapy is preferred in many cases because it is efficient and allows patients to avoid the toxicity of chemotherapy, the authors said.

Cemiplimab (Libtayo), pembrolizumab (Keytruda), and nivolumab (Opdivo) are the 3 immune checkpoint inhibitors that have been approved by the FDA for advanced, recurrent, or metastatic SCC.

Still, the authors noted a number of challenges. The first is selecting the most appropriate patients for the therapy. Patients with high TMB and advanced cancers appear to be good fits for immunotherapy, the authors said. Studies have also evaluated whether programmed death-ligand 1 (PD-L1) status might also be a meaningful marker for the suitability of immunotherapy, but the investigators said the data so far are mixed. As such, there is not yet a reliable biomarker with which to identify patients who are good candidates for immunotherapy.

Another key challenge is resistance, either primary or acquired.

“The process of this resistance is really complex and encompasses a broad spectrum of mechanisms with individual differences,” they wrote.

Lastly, they said some patients experience immune-related adverse events, including diarrhea, fatigue, nausea, pruritus, rash, reduced appetite, constipation, and asthenia. Those adverse events can limit a patient’s ability to tolerate immunotherapy.

The investigators concluded by arguing that immunotherapy remains underused in SCC, partly because of concerns about resistance and partly due to the lack of reliable biomarkers.

“Additional advanced studies are needed to overcome the challenges and to propose a combination of treatment modalities so that a higher number of patients can be cured,” they concluded.

Reference

Ansary TM, Hossain MDR, Komine M, Ohtsuki M. Immunotherapy for the treatment of squamous cell carcinoma: potential benefits and challenges. Int J Mol Sci. Published online August 1, 2022. doi:10.3390/ijms23158530