在III期EXCLAIM-2试验中，一线莫博替尼与铂类化疗用于治疗外显子20插入阳性转移性非小细胞肺癌患者的疗效对比
First-Line Mobocertinib Versus Platinum-Based Chemotherapy in Patients With Exon 20 Insertion-Positive Metastatic Non-Small Cell Lung Cancer in the Phase III EXCLAIM-2 Trial.
作者信息
Jänne Pasi A, Wang Bin-Chao, Cho Byoung Chul, Zhao Jun, Li Juan, Hochmair Maximilian, Peters Solange, Besse Benjamin, Pavlakis Nick, Neal Joel W, Kato Terufumi, Wu Yi-Long, Nguyen Danny, Lin Junjing, Lin Jianchang, Vranceanu Florin, Szumski Annette, Lin Huamao M, Fram Robert J, Mok Tony S K
机构信息
Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
Guangdong Lung Cancer Institute, Guangzhou, China.
出版信息
J Clin Oncol. 2025 May;43(13):1553-1563. doi: 10.1200/JCO-24-01269. Epub 2025 Jan 29.
PURPOSE
Mobocertinib is an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that targets exon 20 insertion (ex20ins) mutations in non-small cell lung cancer (NSCLC). This open-label, phase III trial (EXCLAIM-2, ClinicalTrials.gov identifier: NCT04129502) compared mobocertinib versus platinum-based chemotherapy as first-line treatment of ex20ins+ advanced/metastatic NSCLC.
METHODS
Patients with treatment-naive ex20ins+ locally advanced/metastatic NSCLC were randomly assigned 1:1 to mobocertinib 160 mg once daily or pemetrexed plus cisplatin or carboplatin every 3 weeks for four cycles followed by maintenance pemetrexed. The primary end point was progression-free survival (PFS) by blinded independent central review (BICR), with planned interim analysis (IA) after approximately 70% of 227 expected PFS events.
RESULTS
A total of 354 patients were randomly assigned (mobocertinib: n = 179; chemotherapy: n = 175). Baseline characteristics were balanced between arms. At IA (cutoff: April 4, 2023), the median PFS per BICR was 9.6 months in each treatment arm (hazard ratio [HR], 1.04 [95% CI, 0.77 to 1.39]; = .803). The primary end point crossed the prespecified futility boundary (HR > 1). The confirmed objective response rate (95% CI) per BICR was 32% (26 to 40) with mobocertinib versus 30% (24 to 38) with chemotherapy; the median duration of response was 12.0 versus 8.4 months. Quality-of-life assessments indicated clinically meaningful delays in time to deterioration of lung cancer symptoms, cognitive function, and constipation with mobocertinib versus chemotherapy. Grade ≥3 adverse events in >5% of patients (mobocertinib, chemotherapy) were diarrhea (20%, 1%), anemia (6%, 10%), increased lipase (6%, 0%), and decreased neutrophil count (1%, 7%).
CONCLUSION
The EXCLAIM-2 trial did not meet its primary end point. The efficacy of mobocertinib was not superior to platinum-based chemotherapy for first-line treatment of patients with ex20ins+ advanced/metastatic NSCLC.
目的
莫博替尼是一种口服表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，可靶向非小细胞肺癌（NSCLC）中的外显子20插入（ex20ins）突变。这项开放标签的III期试验（EXCLAIM-2，ClinicalTrials.gov标识符：NCT04129502）比较了莫博替尼与铂类化疗作为ex20ins+晚期/转移性NSCLC的一线治疗方案。
方法
既往未接受过治疗的ex20ins+局部晚期/转移性NSCLC患者按1:1随机分配，分别接受莫博替尼160 mg每日一次，或培美曲塞联合顺铂或卡铂，每3周一次，共四个周期，随后接受培美曲塞维持治疗。主要终点是由盲法独立中央审查（BICR）评估的无进展生存期（PFS），计划在预计的227例PFS事件中的约70%发生后进行中期分析（IA）。
结果
共有354例患者被随机分配（莫博替尼组：n = 179；化疗组：n = 175）。两组的基线特征均衡。在IA时（截止日期：2023年4月4日），每个治疗组经BICR评估的中位PFS均为9.6个月（风险比[HR]，1.04[95%CI，0.77至1.39]；P = 0.803）。主要终点越过了预先设定的无效边界（HR > 1）。经BICR评估，莫博替尼组的确认客观缓解率（95%CI）为32%（26%至40%），化疗组为30%（24%至38%）；中位缓解持续时间分别为12.0个月和8.4个月。生活质量评估表明，与化疗相比，莫博替尼在肺癌症状、认知功能和便秘恶化时间方面有临床意义的延迟。>5%患者中发生的≥3级不良事件（莫博替尼组、化疗组）有腹泻（20%，1%）、贫血（6% , 10%）、脂肪酶升高（6%，0%）和中性粒细胞计数降低（1%，7%）。
结论
EXCLAIM-2试验未达到其主要终点。对于ex20ins+晚期/转移性NSCLC患者的一线治疗，莫博替尼的疗效并不优于铂类化疗。
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