Introduction: The efficacy of immune checkpoint inhibitors (ICPi) in BRAF mutant NSCLC is unknown. Methods: Multi‐institutional retrospective chart review identified 39 patients with BRAF mutant NSCLC. The patients were divided into two groups: V600E (group A, n = 21) and non‐V600E (group B, n = 18). Programmed death ligand 1 (PD‐L1) expression, tumor mutational burden (TMB) and microsatellite instability status were assessed in 29 (74%), 11 (28%), and 12 (31%) patients, respectively. Objective response rate, progression‐free survival (PFS) with ICPi, and overall survival were analyzed. Results: High (≥50%), intermediate (1–49%), and no (<1%) PD‐L1 expression was observed in 8 of 19 (42%), 6 of 19 (32%), 5 of 19 (26%), and 5 of 10 (50%), 1 of 10 (10%), and 4 of 10 (40%) cases in groups A and B, respectively. Two tumors in group A showed high TMB (25%); none were microsatellite instability status–high. Twenty‐two patients (group A, n = 12; group B, n = 10) received ICPi. Objective response rate with ICPi was 25% and 33% in groups A and B, respectively (p = 1.0). Median PFS with ICPi was 3.7 months (95% confidence interval [CI]: 1.6–6.6), and 4.1 months (95% CI: 0.1–19.6) in groups A and B, respectively (log‐rank test = 0.81, p = 0.37). Neither BRAF mutation type nor PD‐L1 expression affected the response probability/PFS. Median overall survival was not reached (95% CI: 13–NR) and comprised 21.1 months (95% CI: 1.8–NR) for patients who were and were not exposed to ICPi, respectively (log‐rank test = 5.58, p = 0.018). Conclusions: BRAF mutant NSCLC is associated with high level of PD‐L1 expression, low/intermediate TMB and microsatellite‐stable status. ICPi have favorable activity both in BRAF V600E and BRAF non‐V600E mutant NSCLC.

中文翻译：

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BRAF 突变肺癌：PD-L1 表达、肿瘤突变负荷、微卫星不稳定性状态和对免疫检查点抑制剂的反应

简介：免疫检查点抑制剂 (ICPi) 在 BRAF 突变 NSCLC 中的疗效尚不清楚。方法：多机构回顾性图表审查确定了 39 名 BRAF 突变 NSCLC 患者。患者分为两组：V600E（A组，n = 21）和非V600E（B组，n = 18）。分别在 29 (74%)、11 (28%) 和 12 (31%) 名患者中评估了程序性死亡配体 1 (PD-L1) 表达、肿瘤突变负荷 (TMB) 和微卫星不稳定性状态。分析了客观缓解率、ICPi 的无进展生存期 (PFS) 和总生存期。结果：在 19 人中有 8 人 (42%)、19 人中有 6 人 (32%)、19 人中有 5 人观察到高 (≥50%)、中等 (1–49%) 和无 (<1%) PD-L1 表达(26%) 和 10 例中的​​ 5 例 (50%)、10 例中的​​ 1 例 (10%) 和 A 组和 B 组中 10 例中的​​ 4 例 (40%)。A 组中的两个肿瘤显示出高 TMB（25%）；没有一个是微卫星不稳定状态——高。22 名患者（A 组，n = 12；B 组，n = 10）接受了 ICPi。在 A 组和 B 组中，ICPi 的客观缓解率分别为 25% 和 33%（p = 1.0）。在 A 组和 B 组中，ICPi 的中位 PFS 分别为 3.7 个月（95% 置信区间 [CI]：1.6-6.6）和 4.1 个月（95% CI：0.1-19.6）（对数秩检验 = 0.81，p = 0.37）。BRAF 突变类型和 PD-L1 表达均不影响反应概率/PFS。对于暴露于和未暴露于 ICPi 的患者，中位总生存期未达到（95% CI：13-NR），分别为 21.1 个月（95% CI：1.8-NR）（对数秩检验 = 5.58，p = 0.018）。结论：BRAF 突变 NSCLC 与高水平的 PD-L1 表达、低/中 TMB 和微卫星稳定状态相关。