Dr. Park addresses the current absence of validated predictive biomarkers in cSCC. Unlike cancers with actionable molecular targets (e.g., EGFR-mutated NSCLC, HER2+ breast cancer), treatment decisions in cSCC remain largely clinically driven. PD-L1 expression is not used to guide treatment decisions, as responses occur even in PD-L1-low or -absent patients.
Tumor mutational burden (TMB) is highlighted as an intriguing emerging biomarker. cSCC has one of the highest TMB levels among solid tumors as a consequence of chronic UV damage, which likely underpins its strong immunotherapy responsiveness. However, cSCCs arising from chronic inflammation (e.g., chronic ulcers, burns, Marjolin’s ulcers) have lower TMB and correspondingly weaker responses to immunotherapy. Dr. Singh notes that no TMB testing is required to prescribe cemiplimab, and that C-POST subgroup analyses showed efficacy regardless of PD-1 mutation percentage, though these analyses were not powered to draw firm conclusions.
For immunocompromised patients, particularly solid organ transplant recipients, Dr. Park describes a nuanced approach using the CONTRACT study protocol: cross-tapering immunosuppression to an mTOR inhibitor and administering pulse-dose prednisone alongside cemiplimab. In her experience, this approach has preserved graft function while achieving antitumor responses, though she acknowledges further investigation is needed. She notes that patients with other organ transplants (not kidney) face higher stakes given the lack of a dialysis backup.
