Related Experiment Video
Updated: Mar 22, 2026
Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib
Published on: June 26, 2019
Dabrafenib in patients with BRAF(V600E)-positive advanced non-small-cell lung cancer: a single-arm, multicentre,
David Planchard1, Tae Min Kim2, Julien Mazieres3
1Department of Medical Oncology, Gustave Roussy, Villejuif, France.
Background:
Activating BRAF(V600E) (Val600Glu) mutations are found in about 1-2% of lung adenocarcinomas, which might provide an opportunity for targeted treatment in these patients. Dabrafenib is an oral selective inhibitor of BRAF kinase. We did a trial to assess the clinical activity of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAF(V600E) mutation.
Methods:
In this phase 2, multicentre, non-randomised, open-label study, we enrolled previously treated and untreated patients with stage IV metastatic BRAF(V600E)-positive NSCLC. Patients received oral dabrafenib 150 mg twice daily. The primary endpoint was investigator-assessed overall response, which was assessed in patients who had received at least one dose of dabrafenib; safety was also assessed in this population. The study is ongoing but not enrolling patients in this cohort. This trial is registered with ClinicalTrials.gov, number NCT01336634.
Findings:
Between Aug 3, 2011, and Feb 25, 2014, 84 patients were enrolled, six of whom had not previously received systemic treatment for NSCLC. 26 of the 78 previously treated patients achieved an investigator-assessed overall response (33% [95% CI 23-45]). Four of the six previously untreated patients had an objective response. One patient died from an intracranial haemorrhage that was judged by the investigator to be due to the study drug. Serious adverse events were reported in 35 (42%) of 84 patients. The most frequent grade 3 or worse adverse events were cutaneous squamous-cell carcinoma in ten (12%), asthenia in four (5%), and basal-cell carcinoma in four (5%).
Interpretation:
Dabrafenib showed clinical activity in BRAF(V600E)-positive NSCLC. Our findings suggest that dabrafenib could represent a treatment option for a population of patients with limited therapeutic options.
Funding:
GlaxoSmithKline.
Insights
Dabrafenib demonstrated clinical activity in patients with advanced non-small-cell lung cancer (NSCLC) harboring the BRAF(V600E) mutation, offering a potential new treatment option for this patient group.
Area of Science:
- Oncology
- Molecular targeted therapy
- Genomics in cancer treatment
Background:
- Activating BRAF(V600E) mutations occur in 1-2% of lung adenocarcinomas, presenting a target for therapy.
- Dabrafenib is an oral selective inhibitor targeting the BRAF kinase enzyme.
Purpose of the Study:
- To evaluate the clinical activity and safety of dabrafenib in patients with advanced non-small-cell lung cancer (NSCLC) positive for the BRAF(V600E) mutation.
- Assessing overall response and adverse events in a phase 2 clinical trial.
Main Methods:
- Phase 2, multicenter, non-randomized, open-label study.
- Enrollment of previously treated and untreated patients with stage IV metastatic BRAF(V600E)-positive NSCLC.
- Administration of oral dabrafenib 150 mg twice daily; primary endpoint was investigator-assessed overall response.
Main Results:
- Overall response observed in 33% (26/78) of previously treated patients and 4/6 previously untreated patients.
- Serious adverse events occurred in 42% (35/84) of patients.
- Most frequent grade 3 or worse adverse events included cutaneous squamous-cell carcinoma (12%) and basal-cell carcinoma (5%).
Conclusions:
- Dabrafenib exhibits clinical activity in BRAF(V600E)-positive NSCLC.
- Dabrafenib represents a potential therapeutic option for patients with limited treatment alternatives.
More Related Videos
08:18Analysis of Lymph Node Volume by Ultra-High-Frequency Ultrasound Imaging in the Braf/Pten Genetically Engineered Mouse Model of Melanoma
Published on: September 8, 2021
10:16Employing Digital Droplet PCR to Detect BRAF V600E Mutations in Formalin-fixed Paraffin-embedded Reference Standard Cell Lines
Published on: October 8, 2015