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Abstract
Background Non-overlapping somatic mutations in BRAF, NRAS, or NF1 genes occured in 85% of our metastatic melanoma patients. It is not known whether these mutations affect immunotherapy outcome.
Methods Next-gen sequencing of 324 oncogenes was performed in 73 metastatic melanoma patients. A retrospective review of immunotherapy outcome was performed.1–4
Results BRAF fusions/internal rearrangements, BRAF V600E, NRAS, NF1 mutations and triple-negative genotypes occurred in 6.9%, 30.1%, 17.8%, 32.9%, and 12.3% of patients, respectively. Median potential follow-up was 41.0 months. Patients with BRAF fusion/rearrangement had decreased progression-free and overall survival (p=0.015). The other genotypes each had similar progression-free and overall survival. Patients who achieved a complete remission as their best objective response at 12 months (n=36, 49.3%) were found to have significantly improved survival compared those who failed to achieve a complete remissions (n= 37, 50.7%, p<0.001).
Conclusions The most important determinant of long-term survival was achievement of a complete response by 12 months following immunotherapy. PR and SD were not a stable type of response and generally resulted in progression and death from melanoma. Rare patients with BRAF fusions or rearrangements had decreased progression-free and overall survival following initial immunotherapy. Other BRAF, NRAS or NF1 mutations were not associated with significant differences in outcome.
References
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Ethics Approval This retrospective data analysis was reviewed by the chair of the Western IRB and deemed exempt from full IRB review and informed consent.
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