BRAF-V600 突变型非小细胞肺癌的治疗顺序：一线靶向治疗与一线（化疗 -）免疫治疗

Treatment Sequences in BRAF-V600-Mutated NSCLC: First-Line Targeted Therapy Versus First-Line (Chemo-) Immunotherapy.

作者信息

Wiesweg Marcel, Alaffas Ali, Rasokat Anna, Saalfeld Felix Carl, Rost Maximilian, Assmann Christin, Herster Franziska, Hilbrandt Moritz, Griesinger Frank, Kron Anna, Roeper Julia, Glanemann Franziska, Kropf-Sanchen Cornelia, Reck Martin, Kulhavy Jonas, Stenzinger Albrecht, Wolf Jürgen, Sebastian Martin, Schuler Martin, Wermke Martin, Frost Nikolaj, Kopp Hans-Georg, Christopoulos Petros, Scheffler Matthias

机构信息

Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; National Center for Tumor Diseases (NCT), NCT West, Essen, Germany; nNGM, National Network Genomic Medicine Lung Cancer, Cologne, Germany.

Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany.

出版信息

J Thorac Oncol. 2025 May 8. doi: 10.1016/j.jtho.2025.04.016.

DOI:10.1016/j.jtho.2025.04.016

PMID:40345491

Abstract

BACKGROUND

Targeted treatment of patients with metastatic BRAF-V600-mutated NSCLC using BRAF/MEK-inhibitors is effective but limited by acquired resistance. Patients with BRAF-mutant NSCLC may derive long-lasting benefit from immune checkpoint inhibition with programmed death-1/programmed death-ligand 1 (PD-L1) antibodies (immuno-oncology [IO]). Although IO is the preferred first-line therapy in BRAF-mutated melanoma, the optimal treatment sequence in BRAF-mutated NSCLC is not defined.

METHODS

This retrospective study investigated the clinical outcome of patients with metastatic BRAF-V600-mutated NSCLC diagnosed in the German national Network Genomic Medicine Lung Cancer.

RESULTS

We identified 205 patients with BRAF-V600-mutated NSCLC; 175 patients received first-line therapy with dabrafenib/trametinib (DAB/TRM, 65.1%), IO alone (19.4%), or chemotherapy-IO (15.4%). Overall survival (OS) and time-to-treatment failure of first-line therapy was identical for patients receiving first-line DAB/TRM (median OS 28.0 months) or chemo/IO (27.8 months, hazard ratio [HR] 1.1, p = 0.68). Female patients had superior OS (HR 0.65, p = 0.049, confirmed in multivariate model), which was mainly driven by superior OS of female to that of male patients receiving first-line DAB/TRM (OS HR 0.53, p = 0.015). There was no sex difference in survival of patients receiving IO-based first-line treatment (OS HR 1.02). Surprisingly, high PD-L1 status (tumor proportion score ≥50%) was associated with shortened time-to-treatment failure in first-line treatment (HR 1.83, p = 0.002, confirmed in multivariate models adjusting for sex; OS with nonsignificant trend, HR 1.4), regardless of whether the first-line regimen was IO-based or targeted therapy.

CONCLUSIONS

Targeted or IO-based first-line treatment of BRAF-V600-mutated NSCLC has similar survival outcomes. Sex and PD-L1 status may support decision-making at the individual patient level.

摘要

背景

使用BRAF/MEK抑制剂对转移性BRAF-V600突变的非小细胞肺癌（NSCLC）患者进行靶向治疗是有效的，但会受到获得性耐药的限制。BRAF突变的NSCLC患者可能从程序性死亡-1/程序性死亡配体1（PD-L1）抗体的免疫检查点抑制（免疫肿瘤学[IO]）中获得持久益处。尽管IO是BRAF突变黑色素瘤的首选一线治疗方法，但BRAF突变NSCLC的最佳治疗顺序尚未确定。

方法

这项回顾性研究调查了在德国国家肺癌基因组医学网络中诊断出的转移性BRAF-V600突变NSCLC患者的临床结局。

结果

我们确定了205例BRAF-V600突变的NSCLC患者；175例患者接受了一线治疗，其中使用达拉非尼/曲美替尼（DAB/TRM，65.1%）、单纯IO（19.4%）或化疗联合IO（15.4%）。接受一线DAB/TRM治疗的患者（中位总生存期[OS]为28.0个月）或化疗联合IO治疗的患者（27.8个月，风险比[HR]为1.1，p = 0.68）的一线治疗的总生存期（OS）和治疗失败时间相同。女性患者的OS更佳（HR为0.65，p = 0.049，在多变量模型中得到证实），这主要是由于接受一线DAB/TRM治疗的女性患者的OS优于男性患者（OS HR为0.53，p = 0.015）。接受基于IO的一线治疗的患者的生存率没有性别差异（OS HR为1.02）。令人惊讶的是，高PD-L1状态（肿瘤比例评分≥50%）与一线治疗中缩短的治疗失败时间相关（HR为1.83，p = 0.002，在调整性别的多变量模型中得到证实；OS有非显著趋势，HR为1.4），无论一线治疗方案是基于IO还是靶向治疗。