Immunotherapy Benefit in a Patient With Non-Small Cell Lung Cancer and a Rare BRAF Mutation.

Rebekah Rittberg,Shantanu Banerji,David E Dawe,Gefei Qing,Susan Green

doi:10.7759/cureus.11224

Abstract

Immunotherapy is less effective in non-small cell lung cancer (NSCLC) with driver mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) and some may extrapolate this trend to other driver mutations. Up to 4% of NSCLC cases contain a BRAF mutation. Most BRAF mutations are V600E, and little is known about the impact of treatment in rare BRAF G469A mutations. We present a case of a patient found to have BRAF G469A mutated NSCLC. She was diagnosed with Stage IIIB NSCLC and treated with concurrent chemotherapy and radiation. Post-treatment imaging demonstrated disease progression and she was started on nivolumab, resulting in a dramatic and prolonged response which is ongoing after 76 cycles. Her substantial response and prolonged benefit suggest that BRAF-mutated NSCLC may respond better than EGFR- or ALK-driven disease to immunotherapy. Due to the rarity of specific mutations, this case adds to the limited current published literature on NSCLC harbouring a BRAF G469A mutation and suggests that immunotherapy is a reasonable treatment option.

Highlights

The therapeutic approach to non-small cell lung cancer (NSCLC) has dramatically shifted with identification of targetable driver mutations and the introduction of immune-checkpoint inhibitors (ICI) [1]
Immunotherapy is less effective in non-small cell lung cancer (NSCLC) with driver mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) and some may extrapolate this trend to other driver mutations
We present a case of a patient found to have BRAF G469A mutated NSCLC

Summary

Introduction

The therapeutic approach to non-small cell lung cancer (NSCLC) has dramatically shifted with identification of targetable driver mutations and the introduction of immune-checkpoint inhibitors (ICI) [1]. We present a case of a 61-year-old female, previous smoker, diagnosed with Stage IIIB NSCLC, adenocarcinoma subtype, programmed death-ligand 1 (PD-L1) >50%, ALK translocation, EGFR mutation, and KRAS mutation-negative and de novo BRAF G469A mutated. She was originally treated on a clinical trial with radical radiation (66 Gray in 33 fractions) and concurrent chemotherapy (cisplatin and etoposide), randomized to receive metformin in combination. Post-treatment computed tomography (CT) demonstrated improvement of her right hilar mass, but new 6.0 x 4.4 cm left adrenal mass and 3.1 x 2.5 cm right adrenal mass (Figure 1) She started nivolumab alone, with near-complete response after 33 cycles. B: Near complete resolution of bilateral adrenal masses after 41 months of nivolumab

Discussion

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Findings

Disclosures