PD-1, PD-L1 Agents Improve Outcomes for Cutaneous Squamous Cell Carcinoma: Todd Schlesinger, MD

Following the 2026 Winter Clinical Miami, which took place between February 27 and March 1, The American Journal of Managed Care^® (AJMC^®) spoke with Todd Schlesinger, MD, about his presentation, “Checkpoint Choices in Cutaneous Squamous Cell Carcinoma (cSCC): Case-Based Exploration of the Role of PD-1 and New PD-L1 Inhibitors,” given alongside David M. Miller, MD, PhD.

In part 1 of the interview, he described how cSCC compares with other skin cancers, explained the impact of PD-1 and PD-L1 inhibitors on the treatment landscape, and outlined the immunotherapies currently approved for cSCC.

Schlesinger is the founder and director of both the Dermatology & Laser Center of Charleston and the Clinical Research Center of the Carolinas.

This transcript has been lightly edited for clarity.

AJMC: Can you provide a brief overview of cSCC and how it compares with other skin cancers?

Schlesinger: I think the common myth when you hear of melanoma is that it's the most deadly cancer, but, in reality, there are more deaths from squamous cell carcinoma in the United States each year than melanoma; it's about 15,000 from cSCC and about 7000 or so from melanoma. That's primarily due to the sheer number of patients who have squamous cell carcinoma vs melanoma.

The data have been improved by the fact that we have better reporting through the SEER [Surveillance, Epidemiology, and End Results] database, which is the registry for oncology patients that used to report non-melanoma skin cancers, like basal and squamous cell carcinomas, together. Now, probably since the 90s or later, squamous cell carcinoma is reported independently, so we can keep better track of the number of cases.

Generally, the deaths are much higher from squamous cell carcinoma, so it's very common, but people don't think of it as being as deadly as it really is.

AJMC: How have PD-1 and PD-L1 inhibitors changed the treatment landscape for advanced cSCC?

Schlesinger: For advanced cSCC, immunotherapy has been a game-changer. The first immunotherapy drugs approved in the space were PD-1 inhibitors such as cemiplimab (Libtayo; Regeneron) and pembrolizumab (Keytruda; Merck), which have been around for a while.

If you go back to what we had before, we actually never had something systemic approved for continuous squamous cell carcinoma. People would use traditional chemotherapy options, none of which were approved, and we had very poor outcomes when it came to the objective response rates, including complete and partial responses.

Immunotherapy has completely changed the paradigm, not only for cSCC but also for other types of cancer, for which immunotherapy has made a big difference in outcomes. It's a different safety profile, but the bottom line is we have definitely been able to increase the response rates for skin-derived squamous cell carcinoma.

AJMC: Which agents are currently approved for cSCC?

Schlesinger: The 3 drugs that are approved now in the cSCC space are pembrolizumab, cemiplimab, and cosibelimab (Unloxcyt; Checkpoint Therapeutics, Inc.). Pembrolizumab and cemiplimab operate by interacting with the PD-1 receptor on the surface of the T cell. Cosibelimab interacts with the PD-L1 ligand on the surface of tumor cells.

Reference

Schlesinger T, Miller DM. Checkpoint choices in cutaneous squamous cell carcinoma (cSCC): case-based exploration of the role of PD-1 and new PD-L1 inhibitors. Presented at: 2026 Winter Clinical Miami; February 27-March 1, 2026; Miami, Florida.