Natural Disease History, Outcomes, and Co-mutations in a Series of Patients With BRAF-Mutated Non-small-cell Lung Cancer

Clin Lung Cancer. 2019 Mar;20(2):e208-e217. doi: 10.1016/j.cllc.2018.10.003. Epub 2018 Oct 23.

Abstract

Background: BRAF mutations occur in 1% to 4% of non-small-cell lung cancer (NSCLC) cases. Previous retrospective studies have reported similar outcomes for BRAF-mutated NSCLC as compared with wild-type tumors without a known driver mutation or tumors harboring other mutations. However, select cases of prolonged survival have also been described, and thus, the natural history of BRAF-mutated NSCLC remains an area of ongoing study. The aim of this series was to describe the natural history, clinical outcomes, and occurrence of co-mutations in patients with BRAF-mutated NSCLC.

Patients and methods: Patients with BRAF-mutated NSCLC seen at Stanford University Medical Center from January 1, 2006 through July 31, 2015 were reviewed. The Kaplan-Meier method was used to calculate median overall survival, and the generalized Wilcoxon test was used to compare median survivals across subgroups of patients.

Results: Within a cohort of 18 patients with BRAF-mutated NSCLC, V600E mutations were most common (72%; 13/18). Clinicopathologic features were similar between patients with V600E versus non-V600E mutations, although there was a trend toward more patients with non-V600E mutations being heavy smokers (80% vs. 31%; P = .12). Co-occurring mutations in TP53 were identified most commonly (28%; 5/18). The median overall survival for the entire cohort was 40.1 months, and the median survival from the onset of metastases (n = 16) was 28.1 months. Survival rates at 2 and 5 years from the onset of metastases were 56% and 13%, respectively.

Conclusion: The clinical behavior of BRAF-mutated NSCLC is variable, but favorable outcomes can be seen in a subset of patients.

Keywords: BRAF; Next-generation sequencing; Non-small cell lung cancer; Overall survival; V600E.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Mutation / genetics*
  • Proto-Oncogene Proteins B-raf / genetics*
  • Retrospective Studies
  • Survival Analysis
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins B-raf