David Bai writes in AJMC that a recent study by Helgadottir et al. demonstrates that the use of CTLA-4, PD-1, or a combination approach achieved high response rates and improved overall survival in patients with CDKN2A mutations with metastatic melanoma.
CDKN2A is a tumor suppressor gene that has been identified as one of the greatest risk factors for cutaneous melanoma. Patients who carry CDKN2A mutations have a risk of melanoma that is >65-fold increased and a lifetime penetrance of >70 percent. CDKN2A mutation carriers also have poorer melanoma survival rates compared with other patients with melanoma. The CDKN2A deletions and loss of p16 protein from the mutations cause increased tumor proliferation and increased risk of metastases.
In the current era, immunotherapy has redefined cancer treatment and has led to considerably improved overall and progression free survival in multiple cancer types, including melanoma. In their study, Helgadottir et al administered immunotherapy to patients with metastatic melanoma and CDKN2A mutations to determine if survival outcomes improved.
Helgadottir H, Ghiorzo P, van Doorn R, et al. Efficacy of novel immunotherapy regimens in patients with metastatic melanoma with germline CDKN2A mutations [published online October 5, 2018]. J Med Genet. doi: 10.1136/jmedgenet-2018-105610