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Vemurafenib in non-small-cell lung cancer patients with BRAFV600 and BRAFnonV600 mutations
J Mazieres1, C Cropet2, L Montané2
1Thoracic Oncology Unit, IFCT (Intergroupe Français de Cancérologie Thoracique), Respiratory Disease Department, Larrey Hospital, CHU Toulouse, Université Paul Sabatier, Toulouse, France.
Background:
BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort.
Patients And Methods:
Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS).
Results:
Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications.
Conclusion:
Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations.
Trial Registration:
ClinicalTrials.gov identifier: NCT02304809.
Insights
Vemurafenib shows efficacy in non-small-cell lung cancer (NSCLC) with BRAF V600 mutations, but not non-V600 mutations. This finding supports routine BRAF V600 biomarker screening for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Clinical Trials
Background:
- BRAF mutations are present in 1%-5% of non-small-cell lung cancer (NSCLC) cases.
- The clinical impact of specific BRAF mutations in NSCLC remains unclear.
- Vemurafenib is a targeted therapy for cancers with BRAF mutations.
Purpose of the Study:
- To assess the efficacy and safety of vemurafenib in NSCLC patients with various BRAF mutations.
- To evaluate the objective response rate (ORR) and survival outcomes.
- To determine if vemurafenib is effective for different types of BRAF mutations in NSCLC.
Main Methods:
- 118 NSCLC patients with BRAF mutations were enrolled in the AcSé vemurafenib trial.
- Tumor samples were screened for BRAF mutations.
- Patients received vemurafenib 960 mg twice daily, with outcomes assessed using RECIST v1.1 criteria.
Main Results:
- No objective response was observed in the 17 patients with BRAF non-V600 mutations.
- In the 101 patients with BRAF V600 mutations, 43 achieved objective responses (ORR).
- The Bayesian estimated success rate for BRAF V600 was 44.9%, with a 99.9% probability of being ≥30%.
Conclusions:
- Vemurafenib monotherapy is effective for BRAF V600-mutated NSCLC.
- BRAF non-V600 mutations do not respond to vemurafenib.
- Routine BRAF V600 biomarker screening is recommended for NSCLC patients.
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