免疫检查点抑制剂以及基于铂的化学疗法的疗效作为携带HER2突变的非小细胞肺癌患者的第一线治疗：LC-SCRUM-ASIA的结果

Efficacy of immune checkpoint inhibitors plus platinum-based chemotherapy as 1st line treatment for patients with non-small cell lung cancer harboring HER2 mutations: Results from LC-SCRUM-Asia

LUNG CANCER

影响因子:4.40000

分区:医学2区 / 肿瘤学3区呼吸系统3区

发表日期:2024 Nov

作者: Yuki Kato, Hibiki Udagawa, Shingo Matsumoto, Hiroki Izumi, Yuichiro Ohe, Terufumi Kato, Kazumi Nishino, Shingo Miyamoto, Sachiko Kawana, Kenichi Chikamori, Masato Shingyoji, Yuki Sato, Yuji Takada, Ryo Toyozawa, Koichi Azuma, Yu Tanaka, Tetsuya Sakai, Yuji Shibata, Eri Sugiyama, Kaname Nosaki, Yoshitaka Zenke, Shigeki Umemura, Kiyotaka Yoh, Masahiro Seike, Koichi Goto

摘要

据报道，HER2突变发生在所有非小细胞肺癌（NSCLC）的所有病例中的2％-5％。 The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear.Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated.Of the 15,251在LC-SCRUM-ASIA数据库中招募的NSCLC患者，在402例患者中检测到肿瘤HER2突变（2.6％）。 HER2突变的最常见亚型是外显子20插入（79％），随后在频率下是酪氨酸激酶结构域突变以外的Exon20INS（10％）和细胞外域中的突变（7％）。与具有EGFR突变或ALK融合的NSCLC相比，具有HER2突变的NSCLC显示出更高的肿瘤突变负担（TMB）（中位数：4.22 vs. 2.54和2.54和2.52突变）。在402例患者中，有268例患者接受了基于铂的ICIS化学疗法（化学ICI，n = 95）或没有ICI（化学疗法，n = 173）作为第一线治疗。与化学基团相比，化学ICI组的无进展生存期（PFS）明显更长（中值8.5 vs. 6.3个月； HR [95％CI]：0.66 [0.50-0.88]; P <0.005）。多变量分析还确定了ICI的使用，除了基于铂的化学疗法作为PFS的独立预后因素。 There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57-1.12], P = 0.20).Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC.在HER2突变NSCLC患者接受铂基化学疗法的HER2-突变患者中，TMB可能涉及PFS的延长。

Abstract

HER2 mutations are reported to occur in 2%-5% of all cases of non-small cell lung cancer (NSCLC). The clinical outcomes in patients with HER2-mutant NSCLC treated with immune checkpoint inhibitors (ICIs) plus platinum-based chemotherapy as 1st line treatment still remain unclear.Using the large-scale clinico-genomic database of LC-SCRUM-Asia, the clinico-genomic characteristics and therapeutic outcomes of patients with HER2-mutant NSCLC were investigated.Of the 15,251 patients with NSCLC enrolled in the LC-SCRUM-Asia database, tumor HER2 mutations were detected in 402 patients (2.6 %). The most common subtype of HER2 mutations was exon 20 in-frame insertions (79 %), followed in frequency by mutations in the tyrosine kinase domain other than Exon20ins (10 %) and mutations in extracellular domains (7 %). NSCLCs harboring HER2 mutations showed a higher tumor mutation burden (TMB) as compared with NSCLCs harboring EGFR mutations or ALK fusions (median: 4.22 vs. 2.54 and 2.52 mutation per megabase, respectively). Of the 402 patients, 268 patients had received platinum-based chemotherapy with ICIs (Chemo-ICI, n = 95) or without ICI (Chemo-alone, n = 173) as 1st line treatment. The progression-free survival (PFS) was significantly longer in the Chemo-ICI group as compared with the Chemo-alone group (median 8.5 vs. 6.3 months; HR [95 %CI]: 0.66 [0.50-0.88]; P < 0.005). Multivariate analysis identified use of ICIs in addition to platinum-based chemotherapy as an independent favorable prognostic factor for PFS. There was no significant difference in the overall survival between the patients of the Chemo-ICI and Chemo-alone groups (median 31.1 vs. 23.3 months; HR [95 %CI]: 0.80 [0.57-1.12], P = 0.20).Addition of ICIs to platinum-based chemotherapy in 1st line treatment may improve the PFS in patients with HER2-mutant NSCLC. The relatively high TMB might be involved in the prolongation of the PFS in patients with HER2-mutant NSCLC receiving platinum-based chemotherapy with ICIs.