近日，上海交通大学医学院附属胸科医院陆舜团队比较了赛沃替尼联合奥西替尼治疗晚期、EGFR突变阳性、MET-肥大非小细胞肺癌（SACHI）与化疗的效果。相关论文于2026年1月13日发表在《柳叶刀》杂志上。

对于EGFR酪氨酸激酶抑制剂（TKI）治疗进展后MET扩增的EGFR突变阳性非小细胞肺癌（NSCLC）患者，赛沃替尼联合奥西替尼是一种潜在的新疗法。该研究旨在评估在该患者群体中，赛沃替尼联合奥西替尼与标准护理铂基双重化疗的有效性和安全性。

研究组在中国68家医院进行了一项多中心、随机、主动对照、开放标签的3期试验，招募局部晚期或转移性EGFR突变阳性NSCLC和EGFR TKI失败后MET扩增的符合条件的成人，并随机分配（1:1），每天一次口服赛沃替尼-奥西替尼或静脉化疗（培美曲塞加顺铂或卡铂），均为21天周期。中心随机化是通过交互式网络反应系统实施的，该系统采用混合块大小方法，根据脑转移的存在、以前暴露于第三代EGFR TKIs和EGFR突变亚型进行分层。主要终点是根据实体肿瘤1.1版应答评估标准的研究者评估的无进展生存期（PFS），使用分层程序进行测试：首先在第三代EGFR TKI初始人群中进行测试，如果阳性，则在意向治疗（ITT）人群中进行测试。对所有接受至少一剂研究治疗的患者进行了安全性分析。中期分析数据截止日期为2024年8月30日。

2021年10月15日至2024年8月30日，共211名患者入组，106名随机分配到赛沃替尼-奥西替尼组，105名随机分配到化疗组，其中211名患者中有137名（65%）为第三代EGFR TKI-naive （赛沃替尼-奥西替尼组69名，化疗组68名）。赛沃替尼-奥西替尼组106例患者中位年龄为59.4岁（IQR 54.3 - 65.8），女性62例（58%），男性44例（42%）。化疗组105例患者中位年龄为61.9岁（IQR为56.3 ~ 69.1），女性55例（52%），男性50例（48%）。所有参与者都是亚洲人。在第三代EGFR TKI-naive患者中，赛沃替尼-奥西替尼与化疗相比，中位PFS显著延长（9.8个月vs 5.4个月[4.2 - 6.0]；风险比0.34 [0.21 - 0.56];p< 0.0001），ITT人群（8.2个月[6.9 - 11.2]vs 4.5个月[3.0 - 5.4];0.34 [0.23 - 0.49];p< 0.0001）亦是如此。在两组接受研究药物的患者中，发生3级或更严重的治疗不良事件的比例相同（赛沃替尼-奥西替尼组106例患者中有60例[57%]，化疗组96例患者中有55例[57%]）。

研究结果表明，在EGFR TKI治疗进展的EGFR突变阳性、MET扩增的NSCLC患者中，赛沃替尼-奥西替尼联合治疗与化疗相比改善了PFS，同时保持了良好的耐受性。该方案为这种生物标志物选择人群提供了一种潜在的口服治疗选择。

附：英文原文

Title: Savolitinib plus osimertinib versus chemotherapy for advanced, EGFR mutation-positive, MET-amplified non-small-cell lung cancer in China (SACHI): interim analysis of a multicentre, open-label, phase 3 randomised controlled trial

Author: Shun Lu, Jie Wang, Nong Yang, Dongqing Lv, Lijuan Chen, Lin Wu, Xingya Li, Longhua Sun, Yongfeng Yu, Bo Jin, Lin Yang, Yubiao Guo, Haipeng Xu, Tienan Yi, Aiping Zeng, Xiaorong Dong, Jianhua Chen, Ziping Wang, Hongrui Niu, Ying Cheng, Pinhua Pan, Pengbo Deng, Hongming Pan, Xuhong Min, Jun Bai, Laiyu Liu, Tongmei Zhang, Juan Li, Songhua Fan, Michael M Shi, Tony Mok, Weiguo Su, Shun Lu, Jie Wang, Nong Yang, Dongqing Lv, Lijuan Chen, Lin Wu, Xingya Li, Longhua Sun, Yongfeng Yu, Bo Jin, Lin Yang, Yubiao Guo, Haipeng Xu, Tienan Yi, Aiping Zeng, Xiaorong Dong, Jianhua Chen, Ziping Wang, Hongrui Niu, Ying Cheng, Pinhua Pan, Pengbo Deng, Hongming Pan, Xuhong Min, Jun Bai, Laiyu Liu, Tongmei Zhang, Juan Li, Songhua Fan, Michael M. Shi, Tony Mok, Weiguo Su, Feng Ye, Xianling Liu, Jianhua Shi, Jiwei Liu, Qisen Guo, Weihua Yang, Junfang Tang, Shundong Cang, Ou Jiang, Jian Fang, Guohua Yu, Lijun Wang, Xibin Zhuang, Zhigang Han, Yiping Zhang, Zhengbo Song, Baogang Liu, Buhai Wang, Jianying Zhou, Wei Gu, Hongcheng Wu, Zhiwei Lu, Yan Yang, Wen Dong, Xiuhua Fu, Youling Gong, Jinhuo Lai, Ping Sun, Yingying Du, Zhihua Liu, Diansheng Zhong, Kaihua Lu, Jianghong Wang, Zhaohong Chen, Xiujie Cui, Zhengxiang Han, Yu Yao, Fang Zhang, Yunchao Huang, Haichuan Su, Zhennan Yi, Lin Li, Tongjian Cui, Puhan Lu, Xiangdong Wang, Jie Yu, Huan Yan, Xian Luo, Yongxin Ren

Issue&Volume: 2026-01-13

Abstract:

Background

Savolitinib combined with osimertinib is a potential novel therapy for patients with EGFR mutation-positive non-small-cell lung cancer (NSCLC) harbouring MET amplification after progression on EGFR tyrosine kinase inhibitor (TKI) therapy. We aimed to evaluate the efficacy and safety of savolitinib–osimertinib versus standard of care platinum-based doublet chemotherapy in this patient population.

Methods

SACHI was a multicentre, randomised, active-controlled, open-label, phase 3 trial conducted across 68 Chinese hospitals. Eligible adults with locally advanced or metastatic EGFR mutation-positive NSCLC and MET amplification after EGFR TKI failure were randomly assigned (1:1) to once daily oral savolitinib–osimertinib or intravenous chemotherapy (pemetrexed plus either cisplatin or carboplatin), both in 21-day cycles. Central randomisation was implemented through an interactive web-response system with stratification based on the presence of brain metastases, previous exposure to third-generation EGFR TKIs, and EGFR mutation subtype, using a mixed block-size methodology. The primary endpoint, investigator-assessed progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumours version 1.1, was tested using a hierarchical procedure: first in the third-generation EGFR TKI-naive population, and if positive, the intention-to-treat (ITT) population. Safety analysis was performed in all patients who received at least one dose of the study treatment. Interim analysis data cutoff was Aug 30, 2024. This study is registered with ClinicalTrials.gov (NCT05015608) and is complete.

Findings

Between Oct 15, 2021, and Aug 30, 2024, 211 patients were enrolled, 106 were randomly assigned to savolitinib–osimertinib and 105 were randomly assigned to chemotherapy, including 137 (65%) of 211 who were third-generation EGFR TKI-naive (69 in the savolitinib–osimertinib group; 68 in the chemotherapy group). In 106 patients in the savolitinib–osimertinib group, the median age was 59·4 years (IQR 54·3–65·8), 62 (58%) were female, and 44 (42%) were male. In 105 patients in the chemotherapy group, the median age was 61·9 years (IQR 56·3–69·1), 55 (52%) were female, and 50 (48%) were male. All participants were Asian. Median PFS was significantly prolonged with savolitinib–osimertinib versus chemotherapy in the third-generation EGFR TKI-naive (9·8 months [95% CI 6·9–12·5] vs 5·4 months [4·2–6·0]; hazard ratio 0·34 [0·21–0·56]; p<0·0001) and ITT populations (8·2 months [6·9–11·2] vs 4·5 months [3·0–5·4]; 0·34 [0·23–0·49]; p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in the same proportion of patients in both groups who received the study drugs (60 [57%] of 106 patients in the savolitinib–osimertinib group and 55 [57%] of 96 patients in the chemotherapy group).

Interpretation

The savolitinib–osimertinib combination improved PFS versus chemotherapy in patients with EGFR mutation-positive, MET-amplified NSCLC that had progressed on EGFR TKI therapy, while maintaining a favourable tolerability profile. This regimen offers a potential oral treatment option for this biomarker-selected population.

DOI: 10.1016/S0140-6736(25)01811-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01811-2/abstract