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.
Robert C, Ribas A, Hamid O, et al. Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma. J Clin Oncol. 2018;36(17):1668−1674.
Perez L, Samlowski W, Lopez-Flores R. Outcome of Elective Checkpoint Inhibitor Discontinuation in Patients with Metastatic Melanoma Who Achieved a Complete Remission: Real-World Data. Biomedicines. 2022;10(5):1144.
Samlowski W, Adajar C. Cautious addition of targeted therapy to PD-1 inhibitors after initial progression of BRAF mutant metastatic melanoma on checkpoint inhibitor therapy. BMC Cancer. 2021;21(1):1187−1199.
Hilts A, Samlowski W. Cautious Addition of MEK Inhibitors to PD-1 Antibody Treatment in Patients with NRAS or NF1 Mutant Metastatic Melanoma Failing Initial Immunotherapy. Annals of Case Reports. 2022;7(2):795−805
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