Overview

• The Cancer Research–published study examined tumor samples from 30 melanoma patients who failed immune checkpoint inhibitors and found NF1 mutations in 40% of resistant cases.
• Molecular analyses revealed that NF1-mutant melanoma cells depend on heightened EGFR pathway activity for survival compared with other mutation profiles.
• Preclinical tests in cell cultures and mouse xenografts showed that FDA-approved EGFR inhibitors cetuximab and afatinib selectively halted growth of NF1-mutant tumors.
• NF1 mutations are estimated to occur in about 27% of all melanoma cases and are overrepresented in tumors refractory to current immunotherapies.
• Investigators are launching early-phase clinical trials to assess the safety and efficacy of EGFR inhibitors alone or alongside immunotherapies for NF1-mutant melanoma.