In the last 5 years, the one-year overall survival for patients with advanced melanoma has risen from 25% to over 70% due the development of two distinct therapies. The first treatment activates anti-tumour immune responses by inhibiting immune checkpoints and the second strategy targets the mitogen-activated protein (MAPK) kinase pathway.
Targeting MAPK with combined BRAF and MEK inhibitors is the first-line standard of care for the 40% of Australian patients with BRAFV600-mutant melanoma, and although 70% will respond, only 20% will have responses lasting more than 3 years. Immune checkpoint inhibitors produce longer-lasting responses but lower response rates and the 30-40% of patients who respond to anti-PD1 immunotherapy will develop resistance and progress within 12-24 months.
Currently we do not know how to accurately identify patients who will respond to immunotherapy, and we have no predictive strategy for selecting novel combination therapies for patients who acquire resistance. Our recent work explores the relationship between pre-treatment and early on treatment circulating tumour DNA and outcome in melanoma patients treated with anti-PD1 inhibitors.