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Updated: Jan 21, 2026

Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Therapeutic outcomes in non-small cell lung cancer with BRAF mutations: a single institution, retrospective cohort
Irena Tan1, Thomas E Stinchcombe2,3, Neal E Ready2,3
1Department of Internal Medicine, Duke University Medical Center, Durham, NC, USA.
Background:
Data describing therapeutic outcomes in patients with non-small cell lung cancers (NSCLC) with BRAF mutations remains limited.
Methods:
We conducted a retrospective cohort study of 31 patients with metastatic NSCLC treated at Duke University Hospital who had been identified by next-generation sequencing methods to bear a BRAF mutation in their tumor in order to evaluate clinical response to immunotherapy and chemotherapy.
Results:
Sixty-five percent of patients identified in this cohort were current or former smokers. Fourteen (45.2%) of patients had a BRAF V600E mutation and 17 (54.8%) had a non-V600E mutation. Median progression-free survival (PFS) in the 23 patients who received first-line chemotherapy was 6.4 months [95% confidence interval (CI), 2.3 to 13.0]. Overall survival (OS) in patients who received first-line chemotherapy showed a median survival of 18 months (95% CI, 7.4 to 28.6). OS comparing patients who had never received immunotherapy at any point was 18.4 months (95% CI, 4.1 to NE) compared to 19.0 months (95% CI, 9.9 to 28.6) in those who had received immunotherapy. We did not find a statistically significant difference in OS in patients with BRAF V600E, BRAF amplification, or non-V600E mutations. There was also no difference in OS in patients treated with targeted BRAF inhibitors compared to those who were not treated with targeted BRAF inhibitors.
Conclusions:
We describe therapeutic outcomes for patients with metastatic NSCLC with BRAF mutations treated with either cytotoxic chemotherapy or immunotherapy. Although the sample size is small, the survival curves do not suggest improved clinical activity in this population when treated with immunotherapy.
Insights
Outcomes for non-small cell lung cancer (NSCLC) with BRAF mutations treated with chemotherapy or immunotherapy are described. This small study found no clear benefit of immunotherapy over chemotherapy in this patient group.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Limited data exists on therapeutic outcomes for non-small cell lung cancer (NSCLC) patients with BRAF mutations.
- BRAF mutations are an important target in various cancers, but their impact on NSCLC treatment response is not fully understood.
Purpose of the Study:
- To evaluate the clinical response to immunotherapy and chemotherapy in patients with metastatic NSCLC harboring BRAF mutations.
- To describe therapeutic outcomes in this specific patient population.
Main Methods:
- A retrospective cohort study was conducted involving 31 patients with metastatic NSCLC and BRAF mutations.
- Tumor samples were analyzed using next-generation sequencing to identify BRAF mutations.
- Patients received either first-line chemotherapy or immunotherapy.
Main Results:
- Of the 31 patients, 45.2% had a BRAF V600E mutation and 54.8% had a non-V600E mutation.
- Median progression-free survival (PFS) for patients receiving first-line chemotherapy was 6.4 months.
- Overall survival (OS) did not significantly differ between patients with different BRAF mutation types or between those treated with or without targeted BRAF inhibitors. Immunotherapy did not show improved clinical activity.
Conclusions:
- Therapeutic outcomes for metastatic NSCLC patients with BRAF mutations treated with chemotherapy or immunotherapy were described.
- Despite the small sample size, survival data did not indicate superior clinical activity for immunotherapy in this population.
- Further research with larger cohorts is needed to fully elucidate optimal treatment strategies.
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