BRAF 突变状态与局部晚期可切除和转移性 NSCLC 的生存结果相关。
BRAF mutational status is associated with survival outcomes in locally advanced resectable and metastatic NSCLC.
发表日期：2024 Jun 26
作者：
Mariano Provencio, Lucía Robado de Lope, Roberto Serna-Blasco, Ernest Nadal, Pilar Diz Tain, Bartomeu Massuti, José Luis González-Larriba, Amelia Insa, Alfredo Sánchez-Hernández, Joaquín Casal-Rubio, Rosario García-Campelo, Silvia Sequero López, Jacobo Rogado, Alex Martínez-Martí, Joaquim Bosch-Barrera, Reyes Bernabé, Sergio Vázquez Estévez, Santiago Ponce, Javier de Castro, Juan Coves Sarto, Noemí Reguart, Manuel Dómine, Andrés Aguilar, Margarita Majem, Anna Estival, Silvia Peña Cabia, Ana López Martín, María Ángeles Sala González, Manuel Cobo, Carlos Camps, Isidoro Barneto, Virginia Calvo, Ana Collazo-Lorduy, Alberto Cruz-Bermúdez, Atocha Romero
来源：
LUNG CANCER
摘要：
基于免疫疗法的治疗已在晚期和局部晚期非小细胞肺癌（NSCLC）患者中表现出高效。 BRAF 突变影响一小部分但很重要的 NSCLC。这些疗法在该亚组患者中的疗效尚不清楚。 血浆和组织样本来自 116 名可切除的 IIIA/B 期 NSCLC 患者，包括 NADIM 和 NADIM II 临床试验（NADIM 队列），以及来自包含 84 名 IV 期患者的前瞻性学术队列通过下一代测序对 NSCLC 患者（BLI-O 队列）进行分析。p.G464E、p.G466R、p.G466V、p.G469V、p.L597Q、p.T599I、p.V600E (n = 2)在 NADIM 队列中的四个 (3.45%) 样本中发现了 BRAF 突变，所有这些样本都是接受新辅助化学免疫疗法 (CH-IO) 治疗的病例，在 BLI-O 队列中的四个 (4.76%) 样本中发现了 BRAF 突变，这些样本对应于接受治疗的病例一线免疫疗法 (n = 2) 或 CH-IO (n = 2)。所有这些患者都还活着，并且在数据截止时没有疾病证据。相反，BLI-O 队列中患有 BRAF 野生型 (wt) 肿瘤的患者的中位无进展生存期 (PFS) 为 5.49 个月，中位总生存期 (OS) 为 12.00 个月（P-LogRank = 0.013 和 0.046） ， 分别）。同样，NADIM 队列中 BRAF-wt 肿瘤患者的 36 个月 PFS 和 OS 概率分别为 60.5% 和 76.1%。 BRAF 阳性肿瘤患者 (n = 4) 新辅助 CH-IO 后的病理完全缓解 (pCR) 率为 100%，而 BRAF-wt 人群的 pCR 率为 44.3%（RR：2.26；95% CI） ：1.78-2.85；P < 0.001）。BRAF 突变可能是接受免疫治疗的晚期和局部晚期 NSCLC 患者的良好预后因素。版权所有 © 2024 作者。由 Elsevier B.V. 出版。保留所有权利。
Immunotherapy-based treatments have demonstrated high efficacy in patients with advanced and locally advanced non-small-cell lung cancer (NSCLC). BRAF mutations affect a small but significant fraction of NSCLC. The efficacy of these therapies in this subgroup of patients is unknown.Plasma and tissue samples from 116 resectable stage IIIA/B NSCLC patients, included in NADIM and NADIM II clinical trials (NADIM cohort), and from a prospective academic cohort with 84 stage IV NSCLC patients (BLI-O cohort), were analyzed by next-generation sequencing.The p.G464E, p.G466R, p.G466V, p.G469V, p.L597Q, p.T599I, p.V600E (n = 2) BRAF mutations, were identified in four (3.45 %) samples from the NADIM cohort, all of which were cases treated with neoadjuvant chemoimmunotherapy (CH-IO), and four (4.76 %) samples from the BLI-O cohort, corresponding to cases treated with first-line immunotherapy (n = 2) or CH-IO (n = 2). All these patients were alive and had no evidence of disease at data cut-off. Conversely, patients with BRAF wild-type (wt) tumors in the BLI-O cohort had a median progression-free survival (PFS) of 5.49 months and a median overall survival (OS) of 12.00 months (P-LogRank = 0.013 and 0.046, respectively). Likewise, PFS and OS probabilities at 36 months were 60.5 % and 76.1 % for patients with BRAF-wt tumors in the NADIM cohort. The pathological complete response (pCR) rate after neoadjuvant CH-IO in patients with BRAF-positive tumors (n = 4) was 100 %, whereas the pCR rate in the BRAF-wt population was 44.3 % (RR: 2.26; 95 % CI: 1.78-2.85; P < 0.001).BRAF mutations may be a good prognostic factor for advanced and locally advanced NSCLC patients undergoing immunotherapy-based treatments.Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.