Patients With BRAF-Mutant NSCLC May Not Benefit From Immune Checkpoint Inhibitors: A Population-Based Study

Chenxing Zhang; Chenyue Zhang; Jiamao Lin; Zhenxiang Li; Haiyong Wang

doi:10.1016/j.jtocrr.2020.100006

Patients With BRAF-Mutant NSCLC May Not Benefit From Immune Checkpoint Inhibitors: A Population-Based Study

JTO Clin Res Rep. 2020 Feb 11;1(1):100006. doi: 10.1016/j.jtocrr.2020.100006. eCollection 2020 Mar.

Authors

Chenxing Zhang¹, Chenyue Zhang², Jiamao Lin³, Zhenxiang Li³, Haiyong Wang³

Affiliations

¹ Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
² Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, People's Republic of China.
³ Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China.

Abstract

Introduction: There is no consensus on whether immune checkpoint inhibitors (ICIs) would offer comparable benefit in mutant-BRAF NSCLC. We, therefore, conducted a study to ascertain the role of ICIs in mutant-BRAF NSCLC.

Methods: Records of 4178 patients and 4462 samples from 15 studies were collected using the database from www.cbioportal.org. The role of BRAF mutation on the overall survival (OS) was analyzed in patients with NSCLC treated with ICIs. Kaplan-Meier analysis was used to calculate OS and the log rank test was used to compare the survival.

Results: Of the patients, 6.1% had the BRAF mutation. Mutations and copy numbers differed by sex. The programmed death ligand 1 expression was higher in patients with the wild-type BRAF compared with those with the BRAF mutation. BRAF mutation is linked with higher tumor mutational burden (p = 0.009). OS for patients with the ICI-treated mutant-BRAF and wild-type-BRAF NSCLC was 10 months and 11 months, respectively (p = 0.334). Subgroup analyses revealed that the median survival was 14 months in the non-V600E group and 5 months in the V600E group (p = 0.017).

Conclusions: Our results revealed that mutant-BRAF NSCLC was associated with high tumor mutational burden. However, for patients with NSCLC receiving ICIs, OS was prolonged in those who had no V600E mutation compared with those who had V600E mutation.

Keywords: BRAF mutation; Biomarker; Immune checkpoint inhibitor; Non-small cell lung cancer.