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Ref Type Journal Article
PMID (29723688)
Authors Dudnik E, Peled N, Nechushtan H, Wollner M, Onn A, Agbarya A, Moskovitz M, Keren S, Popovits-Hadari N, Urban D, Mishaeli M, Zer A, Allen AM, Rabinovich NM, Rotem O, Kuznetsov T, Shochat T, Roisman LC, Bar J, Israel Lung Cancer Group
Title BRAF Mutant Lung Cancer: Programmed Death Ligand 1 Expression, Tumor Mutational Burden, Microsatellite Instability Status, and Response to Immune Check-Point Inhibitors.
Journal Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Vol 13
Issue 8
Date 2018 08
URL
Abstract Text The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown.Multi-institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non-V600E (group B, n = 18). Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression-free survival (PFS) with ICPi, and overall survival were analyzed.High (≥50%), intermediate (1-49%), and no (<1%) PD-L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status-high. Twenty-two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6-6.6), and 4.1 months (95% CI: 0.1-19.6) in groups A and B, respectively (log-rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD-L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13-NR) and comprised 21.1 months (95% CI: 1.8-NR) for patients who were and were not exposed to ICPi, respectively (log-rank test = 5.58, p = 0.018).BRAF mutant NSCLC is associated with high level of PD-L1 expression, low/intermediate TMB and microsatellite-stable status. ICPi have favorable activity both in BRAF V600E and BRAF non-V600E mutant NSCLC.

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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
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
BRAF V600E lung non-small cell carcinoma not predictive Nivolumab Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). 29723688
BRAF V600E lung non-small cell carcinoma not predictive Atezolizumab Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab) compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). 29723688
BRAF V600E lung non-small cell carcinoma not predictive Pembrolizumab Clinical Study - Cohort Actionable In a retrospective analysis, non-small cell lung cancer patients harboring BRAF V600E did not demonstrate a significantly different response to treatment with either Keytruda (pembrolizumab), Opdivo (nivolumab), or Tecentriq (atezolizumab), compared to patients with BRAF non-V600E mutations, demonstrating an objective response rate of 25% (3/12) vs 33% (3/9) (p=1.0) and median progression-free survival of 3.7 months vs 4.1 months (p=0.37) (PMID: 29723688). 29723688