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Ref Type Journal Article
PMID (26200454)
Authors Gautschi O, Milia J, Cabarrou B, Bluthgen MV, Besse B, Smit EF, Wolf J, Peters S, Früh M, Koeberle D, Oulkhouir Y, Schuler M, Curioni-Fontecedro A, Huret B, Kerjouan M, Michels S, Pall G, Rothschild S, Schmid-Bindert G, Scheffler M, Veillon R, Wannesson L, Diebold J, Zalcman G, Filleron T, Mazières J
Title Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort.
Journal Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Vol 10
Issue 10
Date 2015 Oct
URL
Abstract Text Approximately 2% of lung adenocarcinomas have BRAF (v-Raf murine sarcoma viral oncogene homolog B) mutations, including V600E and other types. Vemurafenib, dabrafenib, and sorafenib as BRAF inhibitors are currently tested in clinical trials, but access for patients is limited. The aim of this study was to document the clinical course of patients treated outside of clinical trials.We conducted a retrospective multicenter cohort study in Europe of patients with advanced BRAF-mutant lung cancer treated with known BRAF inhibitors. Data were anonymized and centrally assessed for age, gender, smoking, histology, stage, local molecular diagnostic results, systemic therapies, and survival. Best response was assessed locally by RECIST1.1.We documented 35 patients treated in 17 centers with vemurafenib, dabrafenib, or sorafenib. Median age was 63 years (range 42-85); gender was balanced; 14 (40%) were never smokers; all (100%) had adenocarcinoma; 29 (83%) had V600E; 6 (17%) had other mutations; one of them had a concomitant KRAS mutation. Thirty (86%) patients had chemotherapy in the first line. Overall survival with first-line therapy was 25.3 months for V600E and 11.8 months for non-V600E. Thirty-one patients received one BRAF inhibitor, and four received a second inhibitor. Overall response rate with BRAF therapy was 53%, and disease control rate was 85%. Median progression-free survival with BRAF therapy was 5.0 months, and overall survival was 10.8 months.These results confirm the activity of targeted therapy in patients with BRAF-mutant lung adenocarcinoma. Further trials are warranted to study combination therapies and drug resistance mechanisms.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
BRAF G469L missense unknown BRAF G469L lies within the protein kinase domain of the Braf protein (UniProt.org). G469L has been identified in the scientific literature (PMID: 24035431, PMID: 26301799, PMID: 26200454), but has not been biochemically characterized and therefore, its effect on Braf protein function is unknown (PubMed, May 2022).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF G596V lung non-small cell carcinoma predicted - sensitive Vemurafenib Case Reports/Case Series Actionable In a clinical case study, a non-small cell lung cancer patient harboring BRAF G596V demonstrated a partial response following treatment with Zelboraf (vemurafenib) (PMID: 26200454). 26200454
BRAF V600E lung non-small cell carcinoma sensitive Vemurafenib Clinical Study Actionable In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E achieved an overall response rate of 54% (13/24, 2 complete responses, 11 partial responses, and 10 with stable disease) and a disease control rate of 96% following treatment with Zelboraf (vemurafenib) (PMID: 26200454). 26200454