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

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.

PD‐L1‐negative non‐small cell lung cancer harbouring a rare BRAF mutation with successful treatment of first‐line pembrolizumab plus chemotherapy: A case report and review the literature

“…Our result was similar to those reported by Rittberg et al that demonstrated a prolonged disease control over 4 years with nivolumab monotherapy in a 61‐year‐old patient with advanced NSCLC harbouring a de novo BRAF G469A mutation. However, in this case, PD‐L1 > 50% was observed 27 …”

“…However, in this case, PD-L1 > 50% was observed. 27 In conclusion, we reported a patient with PD-L1-negative NSCLC carrying a rare non-V600E BRAF mutation, who had prolonged response to immunotherapy plus chemotherapy. Further clinical studies are necessary to determine the effectiveness of using immune-based therapy in this specific population.…”

Squamous cell histological transformation in a lung adenocarcinoma patient (hyper) progressing upon immunotherapy

“…In this context, data are scarce, but - in contrast to our case - a previous report on a BRAF G469A mutant NSCLC showed a sustained benefit to second-line nivolumab. 13…”

“…In this context, data are scarce, but -in contrast to our case -a previous report on a BRAF G469A mutant NSCLC showed a sustained benefit to second-line nivolumab. 13 Though rare, NSCLC transformation upon ICI has been described, as shown in Table 1. In all reports, rebiopsy was performed because of disease progression, which was rapid in most cases.…”

The Evolution of BRAF Activation in Non-Small-Cell Lung Cancer

“…Unlike previous study, this study showed that non-V600E had a longer OS than V600E under ICIs treatment ( 72 ). A BRAF G469A mutant NSCLC case obtained a deep and durable response after ICIs treatment, which suggested that BRAF non-V600 mutation may benefit more from immunotherapy than EGFR/ALK-driven mutation in NSCLC ( 73 ). However, in a retrospective, multicenter and real world analysis, 44 of 107 patients with BRAF mutations (V600:26, non-V600:18) received ICIs, with the response rates of 26% in BRAF V600 cohort and 35% in the non-V600 cohort.…”