Shen Lan, Hu Guangyuan, Wang Yan, Zhao Jing, Li Xin, Zhuo Jianmin, Low Grace Kah Mun, Lu Shun
Department of Medical Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Oncology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
BMC Pulm Med. 2025 Aug 1;25(1):364. doi: 10.1186/s12890-025-03826-3.
There is limited data on the unmet needs of advanced non-small cell lung cancer (aNSCLC) patients with epidermal growth factor receptor exon 20 insertion mutations (EGFR exon20ins) in China. The single-arm CHRYSALIS study (NCT02609776) demonstrated durable responses of amivantamab monotherapy among aNSCLC patients with EGFR exon20ins after platinum-based chemotherapy. We aimed to leverage real-world data to describe the unmet needs of these patients and explore the clinical benefits of amivantamab monotherapy through indirect comparison to an external control (EC) from China.
Eligible patients with any systemic anti-cancer therapy (SACT) after the aNSCLC diagnosis were identified from the electronic medical records of three tertiary medical institutions. Clinical outcomes and treatment patterns were compared between patients with exon20ins and common EGFR (cEGFR) mutations. Effectiveness comparison, including real-world progression-free survival (rwPFS), real-world time to next therapy (rwTTNT) and real-world objective response rate (rwORR) was conducted between CHRYSALIS patients and the EC. Propensity score weighting was used to adjust the baseline characteristics between two cohorts. Real-world outcomes were compared between two cohorts using weighted Cox proportional hazards regression models.
EGFR exon20ins patients (n = 60) under SACT had significantly shorter median rwPFS (9.36 vs. 12.42 months) and rwTTNT (9.82 vs. 16.49 months) compared to cEGFR patients (n = 753). The majority of first-line treatment for exon20ins patients was platinum-based regimens (n = 52, 86.7%). Patients from CHRYSALIS and EC cohort were included in the analysis at each qualifying line of therapy (n = 114 and n = 87). Amivantamab-treated patients had significantly improved median rwPFS (6.93 vs. 5.62 months; P = 0.0133), rwTTNT (12.16 vs. 6.01 months; P = 0.0024), and significantly higher rwORR (36.8% vs. 1.0%; P < 0.0001) than EC cohort. Real-world overall survival was numerically longer in amivantamab-treated patients (23.13 vs. 11.63 months; P = 0.1911).
Chinese patients with EGFR exon20ins under SACT had poor clinical outcomes comparing to those with common EGFR mutations in the study. The clinical benefit of amivantamab monotherapy for exon20ins patients was demonstrated through comparing to a real-world EC under standard of care. Amivantamab monotherapy may be considered as a potential effective treatment option for the Chinese patients harboring exon20ins.
关于中国表皮生长因子受体第20外显子插入突变（EGFR exon20ins）的晚期非小细胞肺癌（aNSCLC）患者未满足需求的数据有限。单臂CHRYSALIS研究（NCT02609776）显示，在接受铂类化疗后的aNSCLC且伴有EGFR exon20ins的患者中，阿美替尼单抗单药治疗具有持久疗效。我们旨在利用真实世界数据描述这些患者未满足的需求，并通过与来自中国的外部对照（EC）进行间接比较，探索阿美替尼单抗单药治疗的临床获益。
从三家三级医疗机构的电子病历中识别出在aNSCLC诊断后接受过任何全身抗癌治疗（SACT）的符合条件患者。比较了exon20ins突变患者和常见EGFR（cEGFR）突变患者的临床结局和治疗模式。对CHRYSALIS研究患者和EC进行了疗效比较，包括真实世界无进展生存期（rwPFS）、真实世界下次治疗时间（rwTTNT）和真实世界客观缓解率（rwORR）。采用倾向评分加权法调整两组间的基线特征。使用加权Cox比例风险回归模型比较两组的真实世界结局。
与cEGFR患者（n = 753）相比，接受SACT的EGFR exon20ins患者（n = 60）的中位rwPFS（9.36个月 vs. 12.42个月）和rwTTNT（9.82个月 vs. 16.49个月）显著更短。exon20ins患者的一线治疗大多为铂类方案（n = 52，86.7%）。CHRYSALIS研究和EC队列的患者在每个符合条件的治疗线均纳入分析（n = 114和n = 87）。与EC队列相比，接受阿美替尼单抗治疗的患者中位rwPFS显著改善（6.93个月 vs. 5.62个月；P = 0.0133）、rwTTNT显著改善（12.16个月 vs. 6.01个月；P = 0.0024），且rwORR显著更高（36.8% vs. 1.0%；P < 0.0001）。接受阿美替尼单抗治疗的患者真实世界总生存期在数值上更长（23.13个月 vs. 11.63个月；P = 0.1911）。
在本研究中，接受SACT的中国EGFR exon20ins患者与常见EGFR突变患者相比临床结局较差。通过与标准治疗下的真实世界EC比较，证实了阿美替尼单抗单药治疗对exon20ins患者的临床获益。阿美替尼单抗单药治疗可被视为携带exon20ins的中国患者的一种潜在有效治疗选择。
