拉泽替尼用于治疗携带罕见表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者：一项II期多中心试验。
Lazertinib for Patients with NSCLC Harboring Uncommon EGFR Mutations: A Phase II Multicenter Trial.
作者信息
Park Sehhoon, Ahn Hee Kyung, Lee Seoyoung, Min Young Joo, Kim Jinyong, Jung Hyun Ae, Sun Jong-Mu, Lee Se-Hoon, Ahn Jin Seok, Ahn Myung-Ju, Lee Jii Bum, Lim Sun Min, Kim Hye Ryun, Cho Byoung Chul, Hong Min Hee
机构信息
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; Division of Medical Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea.
出版信息
J Thorac Oncol. 2025 Sep;20(9):1279-1288. doi: 10.1016/j.jtho.2025.05.006. Epub 2025 May 9.
INTRODUCTION
Uncommon EGFR mutations comprise 10% to 20% of all EGFR mutations in NSCLC and generally report reduced responsiveness to EGFR tyrosine kinase inhibitors (TKIs). Lazertinib, a third-generation EGFR-TKI, has found efficacy in common EGFR mutations, but its potential in uncommon mutations remains unexplored. This study investigated the efficacy and safety of lazertinib in patients with NSCLC with uncommon EGFR mutations.
METHOD
This single-arm, multicenter phase II trial enrolled patients with advanced NSCLC harboring uncommon EGFR mutations excluding exon 20 insertions. Patients received lazertinib 240 mg daily until disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety.
RESULTS
Among 36 patients enrolled, the ORR was 50.0% (95% confidence interval [CI]: 34.5%-65.5%), with 18 partial responses, meeting the primary end point. Disease control rate was 88.9% (95% CI: 74.1%-96.2%). Patients with major uncommon mutations (G719X, L861Q, S768I) reported an ORR of 54.8% (17/31). Median PFS was 10.8 months (95% CI: 4.4-19.2), and median DoR was 15.1 months. G719X mutations reported the highest response (ORR 61%, median PFS 20.3 months), followed by S768I (ORR 60%) and L861Q (ORR 58%, median PFS 9.5 months). Treatment-emergent adverse events occurred in all patients, with grade 3 or higher events in 33.3%; most common were rash (47.2%), pruritus (36.1%), and muscle spasms (33.3%).
CONCLUSIONS
Lazertinib reported promising efficacy and a manageable safety profile in patients with NSCLC with uncommon EGFR mutations, particularly for G719X, S768I, and L861Q subtypes. These results suggest lazertinib could be an effective treatment option for this heterogeneous patient population with limited therapeutic alternatives.
引言
非常见表皮生长因子受体（EGFR）突变占非小细胞肺癌（NSCLC）所有EGFR突变的10%至20%，且一般报道显示对EGFR酪氨酸激酶抑制剂（TKIs）的反应性降低。第三代EGFR-TKI拉泽替尼在常见EGFR突变中已显示出疗效，但其在非常见突变中的潜力仍未得到探索。本研究调查了拉泽替尼在患有非常见EGFR突变的NSCLC患者中的疗效和安全性。
方法
这项单臂、多中心II期试验纳入了患有晚期NSCLC且携带非常见EGFR突变（不包括外显子20插入）的患者。患者每天接受240毫克拉泽替尼治疗，直至疾病进展或出现不可接受的毒性。主要终点是根据实体瘤疗效评价标准1.1版确定的客观缓解率（ORR）。次要终点包括无进展生存期（PFS）、总生存期（OS）、缓解持续时间（DoR）和安全性。
结果
在纳入的36例患者中，ORR为50.0%（95%置信区间[CI]：34.5%-65.5%），有18例部分缓解，达到了主要终点。疾病控制率为88.9%（95%CI：74.1%-96.2%）。患有主要非常见突变（G719X、L861Q、S768I）的患者报告的ORR为54.8%（17/31）。中位PFS为10.8个月（95%CI：4.4-19.2），中位DoR为15.1个月。G719X突变的反应率最高（ORR 61%，中位PFS 20.3个月），其次是S768I（ORR 60%）和L861Q（ORR 58%，中位PFS 9.5个月）。所有患者均发生了治疗中出现的不良事件，3级或更高等级的事件发生率为33.3%；最常见的是皮疹（47.2%）、瘙痒（36.1%）和肌肉痉挛（33.3%）。
结论
拉泽替尼在患有非常见EGFR突变的NSCLC患者中显示出有前景的疗效和可控的安全性，特别是对于G719X、S768I和L861Q亚型。这些结果表明，拉泽替尼可能是这一治疗选择有限的异质性患者群体的有效治疗方案。
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