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Updated: Jun 22, 2025
Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC
Mariano Provencio1, Lucía Robado de Lope2, Roberto Serna-Blasco2
1Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain.
Background:
Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown.
Materials And Methods:
Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing.
Results:
The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001).
Conclusion:
BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.
Insights
BRAF mutations may indicate a positive prognosis in non-small-cell lung cancer (NSCLC) patients receiving immunotherapy. Patients with BRAF mutations showed promising survival outcomes and response rates in clinical trials.
Area of Science:
- Oncology
- Genetics
- Immunotherapy
Background:
- Immunotherapy is effective for advanced non-small-cell lung cancer (NSCLC).
- BRAF mutations occur in a subset of NSCLC patients.
- The impact of BRAF mutations on immunotherapy efficacy in NSCLC is not well understood.
Purpose of the Study:
- To investigate the efficacy of immunotherapy in NSCLC patients with BRAF mutations.
- To determine if BRAF mutations are associated with improved outcomes in NSCLC patients treated with immunotherapy.
Main Methods:
- Next-generation sequencing was used to analyze plasma and tissue samples from NSCLC patients in the NADIM and BLI-O cohorts.
- Patients received either neoadjuvant chemoimmunotherapy (CH-IO) or first-line immunotherapy.
- Outcomes including progression-free survival (PFS), overall survival (OS), and pathological complete response (pCR) were assessed.
Main Results:
- BRAF mutations were identified in 3.45% of the NADIM cohort and 4.76% of the BLI-O cohort.
- All patients with BRAF mutations were alive with no evidence of disease at data cut-off.
- BRAF-mutated NSCLC patients treated with neoadjuvant CH-IO achieved a 100% pCR rate, compared to 44.3% in BRAF wild-type patients.
Conclusions:
- BRAF mutations may serve as a favorable prognostic marker in advanced NSCLC patients undergoing immunotherapy.
- The presence of BRAF mutations is associated with superior treatment response and survival outcomes.
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