Anti-programmed cell death 1's effects on cutaneous squamous cell carcinoma in patients with metastatic melanoma

Introduction/Background: The last decade has been the golden age in the development of systemic anti-melanoma therapies. Anti-programmed cell death 1 (anti-PD1) has been shown as an effective treatment of extracutaneous squamous cell carcinomas. We aim to compare the rates of cutaneous SCC (cuSCC) in patients with metastatic melanoma treated with BRAF inhibitors monotherapy (BRAFi), dabrafenib and trametinib combination (CombiDT) or anti-PD1, with a group of control patients on no therapy.
Methods: We reviewed the medical records of all Stage IIIC or IV melanoma patients on BRAFi, CombiDT or anti-PD1 seen at Westmead Hospital, Australia. For the controls, we reviewed the records of all patients seen at the High Risk Melanoma Clinic, Westmead Hospital with a personal history of at least one melanoma or CDKNA2 gene mutation.
Results: 342 patients were included: 134 on BRAFi, 69 on CombiDT, 82 on anti-PD1 and 57 controls. BRAFi had the highest rate of cuSCC development (23.9% of patients, 90 cuSCC), followed by anti-PD1 (7.3% of patients, 8 cuSCC) and CombiDT (2.9% of patients, 2 cuSCC). There were higher rates of cuSCC in patients on BRAFi (p<0.001) compared to controls. CombiDT and anti-PD1 had lower rates of cuSCC compared to BRAFi (both p<0.001). CombiDT and anti-PD1 did not show any differences in cuSCC rate when compared to controls.
Conclusion: Interestingly, despite the fact that anti-PD1 has shown efficacy in treating extra-cutaneous squamous cell carcinoma, we did not find anti-PD1 to reduce the rate of cuSCC compared to a group of controls with similar sporadic risks.

Dr. Cathy Zhao