• Pei Meng, Bart Koopman, Klaas Kok, Arja Ter Elst, Ed Schuuring, Léon C van Kempen, Wim Timens, T Jeroen N Hiltermann, GroenHarry J MHJMDepartment of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, the Netherlands., Anke van den Berg, and Anthonie J van der Wekken.
• Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, the Netherlands.
• Lung Cancer. 2020 Aug 1; 146: 358-361.

IntroductionPrevious studies have reported an acquiredBRAF V600E mutation as a potential resistance mechanism to osimertinib treatment in advanced NSCLC patients with an activating mutation in EGFR. However, the therapeutic effect of combining dabrafenib and trametinib with osimertinib remains unclear. Here we report treatment efficacy in two cases with acquired BRAF V600E mutations.MethodsTwo patients with anEGFR exon 19 deletion and a T790 M mutation, both treated with osimertinib, acquired a BRAF V600E mutation at disease progression. Following the recommendation of the molecular tumor board, a concurrent combination of dabrafenib and trametinib plus osimertinib was administered.ResultsBecause of toxicity, one patient ultimately received a reduced dose of dabrafenib and trametinib combined with a normal dose of osimertinib. Clinical response in this patient lasted for 13.4 months. Re-biopsy upon tumor progression revealed loss ofBRAF V600E and emergence of EGFR C797S. The other patient, treated with full doses of the combined therapy, had progression with metastases in lung and brain one month after starting therapy.ConclusionBRAF V600E may be a resistance mechanism induced by osimertinib in EGFR-mutated advanced NSCLC. Combined treatment using dabrafenib/trametinib concurrently with osimertinib needs to be explored for osimertinib-induced BRAF V600E mutation.Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

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