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565 Effect of non-overlapping mutations in BRAF, NRAS or NF1 on long-term survival after checkpoint inhibitor-based treatment for metastatic melanoma
  1. Wolfram Samlowski1,
  2. Alyssa Panning2 and
  3. Gabriel Allred3
  1. 1Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
  2. 2University of Nevada, Las Vegas, NV, USA
  3. 3Gables Statistical Consulting, Las Vegas, NV, USA


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.


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  2. 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.

  3. 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.

  4. 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

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.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See

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