免疫检查点抑制剂联合铂类化疗作为HER2突变非小细胞肺癌患者一线治疗的疗效：LC-SCRUM-Asia的研究结果

IF 4.5 2区医学 Q1 ONCOLOGY

Lung Cancer Pub Date : 2024-10-13 DOI:10.1016/j.lungcan.2024.107992

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 , Koichi Goto

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引用次数: 0

摘要

导言据报道，在所有非小细胞肺癌（NSCLC）病例中，有2%-5%发生了HER2突变。HER2突变的NSCLC患者在接受免疫检查点抑制剂（ICIs）加铂类化疗作为一线治疗后的临床疗效仍不明确。结果在LC-SCRUM-Asia数据库登记的15251名NSCLC患者中，有402名患者（2.6%）检测到肿瘤HER2突变。最常见的HER2突变亚型是外显子20框架内插入（79%），其次是外显子20ins以外的酪氨酸激酶结构域突变（10%）和胞外结构域突变（7%）。与携带表皮生长因子受体（EGFR）突变或ALK融合的NSCLC相比，携带HER2突变的NSCLC显示出更高的肿瘤突变负荷（TMB）（中位数：每兆碱基突变数分别为4.22对2.54和2.52）。在402名患者中，有268名患者接受了以铂为基础的化疗，同时使用ICIs（Chemo-ICI，n = 95）或不使用ICIs（Chemo-alone，n = 173）作为一线治疗。与单用化疗组相比，化疗-ICI 组的无进展生存期（PFS）明显更长（中位 8.5 个月对 6.3 个月；HR [95 %CI]：0.66 [0.50-0.88]；P < 0.005）。多变量分析发现，在铂类化疗基础上使用 ICIs 是 PFS 的独立有利预后因素。化疗组和单用化疗组患者的总生存期无明显差异（中位 31.1 个月 vs. 23.3 个月；HR [95 %CI]：0.80 [0.57-1.12]，P = 0.20）。在铂类化疗中加入 ICIs 可改善 HER2 突变 NSCLC 患者的 PFS，TMB 相对较高可能与 HER2 突变 NSCLC 患者接受 ICIs 化疗的 PFS 延长有关。

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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

Introduction

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.

Methods

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.

Results

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).

Conclusions

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.

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来源期刊

Lung Cancer 医学-呼吸系统

CiteScore

9.40

自引率

3.80%

发文量

407

审稿时长

25 days

期刊介绍： Lung Cancer is an international publication covering the clinical, translational and basic science of malignancies of the lung and chest region.Original research articles, early reports, review articles, editorials and correspondence covering the prevention, epidemiology and etiology, basic biology, pathology, clinical assessment, surgery, chemotherapy, radiotherapy, combined treatment modalities, other treatment modalities and outcomes of lung cancer are welcome.