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- Title
Efficacy and Safety of Trametinib in Non‐V600 BRAF Mutant Melanoma: A Phase II Study.
- Authors
Nebhan, Caroline A.; Johnson, Douglas B.; Sullivan, Ryan J.; Amaria, Roda N.; Flaherty, Keith T.; Sosman, Jeffrey A.; Davies, Michael A.
- Abstract
Lessons Learned: This study suggests that trametinib has significant clinical activity in non‐V600 BRAF mutation and BRAF fusion metastatic melanoma, albeit in a small cohort.All patients with metastatic melanoma should undergo sequencing of the BRAF gene to identify noncanonical BRAF mutations that may indicate benefit from treatment with trametinib. Background: Non‐V600 BRAF mutations and BRAF fusions in aggregate occur in approximately 5% of all melanomas. Inhibition of the mitogen‐activated protein kinase (MAPK) pathway has been implicated as a possible treatment strategy for these patients. Methods: In this open‐label, multicenter, phase II study, patients with advanced melanoma harboring mutations in BRAF outside V600 (non‐V600) or BRAF fusions received trametinib 2.0 mg daily. Patients were divided into cohorts based on the intrinsic catalytic activity of BRAF mutation (high, cohort A; low/unknown, cohort B). The primary endpoint was objective response rate (ORR) for patients in cohort A; secondary endpoints included ORR in cohort B, safety, and survival in both treatment arms. Results: Among all patients, the ORR was 33% (three of nine patients), including 67% in cohort A and 17% in cohort B. Two patients had stable disease as best response, and six patients had some degree of tumor shrinkage. The median progression‐free survival (PFS) was 7.3 months. Treatment‐related adverse events occurred in all patients (100%); most (89%) were grade 1–2. Conclusion: In contrast to recently described tumor‐agnostic studies in a genetically similar population, trametinib had considerable activity in a small population of patients with melanoma harboring BRAF non‐V600 mutations and fusions, providing rationale for sequencing in search of these genomic alterations.
- Subjects
MELANOMA prognosis; THERAPEUTIC use of antineoplastic agents; DRUG efficacy; RESEARCH; GENETIC mutation; CLINICAL trials; SEQUENCE analysis; MELANOMA; ANTINEOPLASTIC agents; MEDICAL cooperation; METASTASIS; CANCER patients; DESCRIPTIVE statistics; MITOGEN-activated protein kinases; CHEMICAL inhibitors
- Publication
Oncologist, 2021, Vol 26, Issue 9, p731
- ISSN
1083-7159
- Publication type
Article
- DOI
10.1002/onco.13795