Related Experiment Video
Updated: Feb 27, 2026
Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research
Published on: March 29, 2024
Retrospective Study of Trametinib in Patients With Advanced NF1-Mutant Melanoma
Lin Wang1, Mohammed Kashani-Sabet2, Prasad Dighe3
1California Pacific Medical Center (CPMC), San Francisco, CA.
Purpose:
Neurofibromin 1 (NF1) mutations, the third most common driver mutation in melanoma, occur in approximately 15% of cases and lead to the constitutive activation of the RAF/MAPK pathway, resulting in cell proliferation and survival. MEK inhibitors can inhibit the RAF/MAPK pathway and potentially induce tumor regression.
Patients And Methods:
We conducted a retrospective study to evaluate the clinical benefit of trametinib in patients with metastatic melanoma harboring an NF1 mutation, using the Institutional Tumor Registry and Melanoma Database. We reviewed the records of all patients with metastatic melanoma whose tumor specimens were analyzed by next-generation sequencing.
Results:
Among 231 patients whose melanoma was analyzed by next-generation sequencing, 34 (14.7%) had an NF1 mutation and four were treated with trametinib. The median age was 77 years; two patients had mucosal melanoma, and two had cutaneous melanoma. Three patients had stage IV disease. All four patients were previously treated with anti-PD1 antibodies, and three were also treated with anti-CTLA4 antibodies. Three (75%) patients experienced initial tumor regression, including one prolonged partial response with a progression-free survival (PFS) duration of 18 months. The other two patients discontinued treatment because of intolerable adverse events, and their tumors subsequently progressed on treatment discontinuation. The median PFS duration was 6 months. Interestingly, the patient with the longest response had the highest variant allele frequency (VAF) of NF1, whereas the early progressor had the lowest VAF. Two of the responders had a primary mucosal melanoma.
Conclusion:
Despite the small number of patients in our study, our findings suggest the promising activity of trametinib in patients with NF1-mutant melanoma, supporting a rationale for prospective studies of MEK inhibitor therapy.
Insights
Trametinib showed promising activity in patients with Neurofibromin 1 (NF1) mutant melanoma, with three of four patients experiencing initial tumor regression. Further prospective studies of MEK inhibitor therapy are warranted.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Neurofibromin 1 (NF1) mutations are a common driver in melanoma (15% of cases), activating the RAF/MAPK pathway and promoting tumor growth.
- MEK inhibitors offer a targeted approach by inhibiting this pathway, potentially leading to tumor regression.
Purpose of the Study:
- To evaluate the clinical benefit and efficacy of trametinib in patients with metastatic melanoma harboring NF1 mutations.
Main Methods:
- Retrospective study of patients with metastatic melanoma and NF1 mutations identified via next-generation sequencing.
- Analysis of clinical data from the Institutional Tumor Registry and Melanoma Database.
Main Results:
- Out of 231 patients, 34 (14.7%) had NF1 mutations; four were treated with trametinib.
- Three of four patients (75%) showed initial tumor regression, with one achieving an 18-month progression-free survival (PFS).
- Median PFS was 6 months; treatment discontinuation due to adverse events occurred in two patients.
Conclusions:
- Trametinib demonstrates promising activity in NF1-mutant melanoma patients.
- Findings support further investigation of MEK inhibitors in this patient population through prospective studies.
