免疫检查点抑制剂联合铂类化疗作为非小细胞肺癌（NSCLC）伴HER2突变患者的一线治疗效果：LC-SCRUM-Asia的研究结果
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
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影响因子:4.4
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
DOI:
10.1016/j.lungcan.2024.107992
摘要
HER2突变发生在所有非小细胞肺癌（NSCLC）病例的2%-5%。在HER2突变NSCLC患者中，使用免疫检查点抑制剂（ICIs）联合铂类化疗作为一线治疗的临床疗效尚不明确。利用LC-SCRUM-Asia的大规模临床-基因组数据库，研究了HER2突变NSCLC患者的临床-基因组特征及治疗结果。在纳入的15,251名NSCLC患者中，检测到402例（2.6%）具有HER2突变。HER2突变中最常见的是外显子20的框内插入（79%），其次是酪氨酸激酶域（非外显子20ins，10%）及胞外结构域突变（7%）。携带HER2突变的NSCLC显示出较高的肿瘤突变负荷（TMB），中位值为4.22比对携带EGFR突变或ALK融合的NSCLC分别为2.54和2.52突变/兆碱基。402例中，268例接受了含ICIs的铂类化疗（Chemo-ICI，n=95）或不含ICIs的铂类化疗（Chemo-alone，n=173）作为一线治疗。无progression-free survival（PFS）显示，Chemo-ICI组的中位无进展生存期显著长于Chemo-alone组（8.5 vs. 6.3个月；HR [95%CI]: 0.66 [0.50-0.88]；P<0.005）。多变量分析确认联合使用ICIs及铂类化疗是PFS的独立有利预后因素。总体生存期（OS）方面，Chemo-ICI组与Chemo-alone组无显著差异（中位31.1 vs. 23.3个月；HR [95%CI]: 0.80 [0.57-1.12]，P=0.20）。在一线治疗中加入ICIs于铂类化疗，有望改善HER2突变NSCLC患者的PFS。较高的TMB可能促使接受铂类化疗联合ICIs的患者PFS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.