EGFR/BRAF/MEK co-inhibition for EGFR-mutated lung adenocarcinoma patients with an acquired BRAFV600E mutation: a case report and review of literature.

Ran Zeng,Yi Xiang,Xianwen Sun,Wei Du,Ranran Dai,Zhiyao Bao,Wei Tang,Beili Gao,Lifeng Luo

doi:10.20517/cdr.2021.98

Abstract

Despite the promising initial anti-tumor efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), most advanced non-small-cell lung cancers (NSCLCs) progress eventually due to therapeutic resistance. V-Raf murine sarcoma viral oncogene homolog B1 (BRAF)V600E mutation has been considered as an uncommon mutation that contributes to acquired resistance for EGFR-TKIs. In the presented case, BRAFV600E mutation was detected as an acquired resistance-mediated mutation in a patient treated with osimertinib (a third-generation EGFR-TKI). The presented patient achieved partial regression and ongoing PFS of four months after the co-inhibition of osimertinib plus dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Our case further enriches the clinical evidence of the efficacy of EGFR/BRAF/MEK co-inhibition in patients with an acquired BRAFV600E mutation, consistent with the review of the literature (eight cases). Additionally, our case highlights the important role of sample type, method, and platform of gene detection in patient management, life quality, and prognosis, as well as the understanding of acquired resistance mechanism.

Highlights

Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small-cell lung cancer (NSCLC) represents the histological subtype of 85% of lung cancer[1]
Great progress has been made in targeting the driver gene mutation for lung adenocarcinoma, a common subtype of NSCLC
Epidermal growth factor receptor (EGFR) mutations occur in 16% of advanced adenocarcinoma Caucasian patients, and the mutation frequency is as high as 61.1% in Asian females[2,3]

Summary

INTRODUCTION

Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small-cell lung cancer (NSCLC) represents the histological subtype of 85% of lung cancer[1]. EGFR-tyrosine kinase inhibitors (TKIs) are the most common targeted therapy available for lung adenocarcinoma, including the first-generation inhibitors erlotinib, gefitinib, and icotinib; the second-generation inhibitor afatinib; and the thirdgeneration inhibition osimertinib[4]. These therapies show promising initial anti-tumor activities, most advanced NSCLC cases eventually progress due to therapeutic resistance, known as acquired resistance (AR). The treatment quickly prompted a stable disease based on criteria in Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and decreased CEA level Five months later, she was diagnosed with drug-induced abnormal liver function (Grade 3) due to increased glutamine transaminase (ALT), aspartate amino transferase (AST), and bilirubin. At the last follow-up (September 2021), her disease evaluation remained stable

DISCUSSION

69 EGFR L858R Male

Findings

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