Multicenter Observational Study on Metastatic Non-Small Cell Lung Cancer Harboring BRAF Mutations: Focus on Clinical Characteristics and Treatment Outcome of V600E and Non-V600E Subgroups (original) (raw)
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Clinical Lung Cancer, 2018
BRAF mutations occur infrequently in non-small-cell lung cancer, and therefore, our understanding of the natural history of tumors harboring these mutations remains limited. In this retrospective study, we report the outcomes, treatment responses, and co-occurring mutations in a series of patients with BRAF-mutated non-small-cell lung cancer. In our cohort, survival rates at 2 and 5 years were 56% and 13%, respectively, suggesting more favorable outcomes in a subset of patients. Background: BRAF mutations occur in 1% to 4% of non-small-cell lung cancer (NSCLC) cases. Previous retrospective studies have reported similar outcomes for BRAF-mutated NSCLC as compared with wild-type tumors without a known driver mutation or tumors harboring other mutations. However, select cases of prolonged survival have also been described, and thus, the natural history of BRAF-mutated NSCLC remains an area of ongoing study. The aim of this series was to describe the natural history, clinical outcomes, and occurrence of co-mutations in patients with BRAF-mutated NSCLC.
BRAF-mutations in non-small cell lung cancer
Lung Cancer, 2014
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Cancer, 2014
(1) PURPOSE-The advent of effective targeted therapy in BRAF V600E mutant lung adenocarcinomas necessitates further exploration of the unique clinical features and behavior of advanced stage BRAF mutant lung adenocarcinomas. (2) PATIENTS AND METHODS-We reviewed data from patients with advanced lung adenocarcinomas enrolled in the Lung Cancer Mutation Consortium whose tumors underwent testing for mutations in EGFR, KRAS, HER2, AKT1, BRAF, MEK1, NRAS, PIK3CA, ALK translocations, and MET amplification. (3) RESULTS-Twenty-one BRAF mutations were identified in 951 patients with adenocarcinomas (2.2%: 95% CI 1.4 to 3.4%); 17 (81%: 95% CI 60 to 92%) were BRAF V600E and 4 were non-BRAF V600E mutations. Among the 733 cases tested for all 10 genes, BRAF mutations were more likely to occur in current or former smokers than most other genotypic abnormalities
Targeted Therapy for Patients with BRAF-Mutant Lung Cancer: Results from the European EURAF Cohort.
INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Cancers
Background: In non-small cell lung cancer (NSCLC), BRAF class 1 alterations are effectively targeted by BRAF inhibitors. Conversely, targeted therapies have very low or absent activity in patients carrying class 2 and 3 alterations. The spectrum of BRAF alterations in NSCLC patients, and their accompanying clinical features, genomic landscape and treatment outcomes have been poorly reported. Patients and methods: We identified BRAF alterations of defined functional class across different tumors through a systematic review. Then, we selected NSCLC patients carrying BRAF alterations, according to the systematic review, in the cBioPortal (cBioPortal cohort) to collect and analyze clinical, biomolecular and survival data. Finally, we identified NSCLC patients carrying BRAF non-V600 mutations enrolled in POPLAR and OAK trials (POPLAR/OAK cohort), extracting clinical and survival data for survival analyses. Results: 100 different BRAF non-V600 alterations were identified through the syste...
Selection Strategies and Practical Application of BRAF V600E-Mutated Non–Small Cell Lung Carcinoma
Cancer Research and Treatment
PurposeThe incidence of BRAF V600E mutation in non-small cell lung carcinoma (NSCLC) is lower than 2%, which poses difficulties in finding legitimate patients for targeted therapy. We investigated the predictive factors pertaining to BRAF V600E and the effectiveness of the VE1 antibody as a screening method for patient selection.Materials and MethodsThe study was designed into two steps. In a first group, BRAF-mutated NSCLCs were identified from sequencing data to determine the features of BRAF V600E mutation. The results of the first group helped the collection of adenocarcinomas with a papillary or micropapillary pattern but without EGFR or ALK alterations as a second group so that the frequency of BRAF V600E mutation could be calculated. The sensitivity and specificity of the VE1 were compared with BRAF V600E status. ResultsAmong 39 BRAF-mutated NSCLCs in the first group, 20 (51%) were V600E. BRAF V600E mutation was more common in female patients and showed no significant correla...
Journal of Thoracic Oncology, 2018
of cycles: 11 (1-68). Most were current or former smokers (94,6%). Only 2,3% had EGFR mutations, and 0,6% ALK rearrangement. PD-L1 immunohistochemistry was only available in 25% of patients (<1%: 36,6%; 1-49%: 39%; >¼50%: 24,4%). After calculating LIPI score, 56,4% were LIPI 0 (good prognosis), 38,5% LIPI 1 (intermediate prognosis), and 5,1% LIPI 2 (poor prognosis). Response rate (RR) was 30,4% and disease control rate (DCR) 52%. The median PFS and OS were 5,6 months (m) (3,9-7,3) and 11,4 m (9,4-13,5). Median OS for good, intermediate, and poor was 14m (95% CI, 11,2-16,7), 6,3m (95% CI, 0,6-12) and 1,8m (95% CI, 0-4,3), respectively (p¼0,0001). LIPI showed correlation with OS in patients with known PD-L1 status and also in those with no information about it. PFS was also correlated (p¼0,004) with LIPI score. A LIPI score of 2 was independently associated with poorer OS (HR 4,9; 95% CI, 2,18-11,1). Conclusion: Our results support the prognostic value of pretreatment LIPI score. dNLR >3 and LDH greater than ULN was correlated with worse outcomes for ICI, regardless of the knowledge of PD-L1 status. This is a useful tool, based on clinical criteria, that can help us in daily practice to identify which patients benefit from ICI.