Data from Impact of BRAF Mutation Class on Disease Characteristics and Clinical Outcomes in BRAF-mutant Lung Cancer

Abstract

<div>AbstractPurpose:<p><i>BRAF</i> mutations are divided into functional classes distinguished by signaling mechanism and kinase activity: V600-mutant kinase-activating monomers (class I), kinase-activating dimers (class II), and kinase-inactivating heterodimers (class III). The relationship between functional class and disease characteristics in BRAF-mutant non–small cell lung cancer (NSCLC) has not been fully explored.</p>Experimental Design:<p>We performed a retrospective analysis of BRAF-mutant NSCLCs treated at 2 institutions from 2005 to 2017 to determine clinicopathologic characteristics, progression-free survival (PFS) on chemotherapy, and overall survival (OS).</p>Results:<p>We identified 236 patients with BRAF-mutant NSCLC (<i>n</i> = 107 class I, <i>n</i> = 75 class II, and <i>n</i> = 54 class III). Patients with class II or III mutations were more likely to have brain metastases (<i>P</i> ≤ 0.01) and <i>RAS</i> coalterations (<i>P</i> ≤ 0.001) than class I. Compared with class I, PFS on chemotherapy was shorter for class II (<i>P</i> = 0.069) and class III (<i>P</i> = 0.034). OS was shorter for class II and III (class I, 40.1 months; class II, 13.9 months; and class III, 15.6 months; I vs. II, <i>P</i> < 0.001; I vs. III, <i>P</i> = 0.023); however, this difference was driven by fewer extrathoracic metastases and higher use of targeted therapies in class I patients. When patients treated with targeted therapy and those with thoracic-only metastases were excluded, there was no difference in OS across the 3 classes.</p>Conclusions:<p>BRAF-mutant NSCLC is a heterogeneous disease that encompasses 3 distinct functional classes. Classes II and III have more aggressive clinical features leading to less favorable outcomes. The distinct biological characteristics of class II and III tumors suggest that class-specific therapies may be necessary to effectively target these molecular subsets.</p></div>