中山大学肿瘤中心张力团队比较了沙西妥珠单抗替鲁莫替康与多西他赛治疗既往治疗的EGFR突变晚期非小细胞肺癌的疗效与安全性。这一研究成果发表在2025年6月5日出版的《英国医学杂志》上。

为了比较沙西妥珠单抗替鲁莫替康（sac-TMT）与多烯紫杉醇治疗局部晚期或转移性表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）患者的疗效和安全性，这些患者先前使用EGFR酪氨酸激酶抑制剂和基于铂的化疗治疗失败，研究组进行了一项多中心、开放标签、随机对照试验。

2023年9月1日至2024年12月31日，在中国设立48个中心，137名成年患者（18-75岁）在之前接受EGFR酪氨酸激酶抑制剂和铂类化疗失败后，患有EGFR突变的晚期或转移性NSCLC。患者被随机分配（2:1），在每个四周周期的第1天和第15天接受囊性TMT（5mg/kg），或在每个三周周期的第一天接受多西他赛（75mg/m²）。多西他赛组的患者在疾病进展时被允许交叉到囊性TMT治疗。

主要终点是由盲法独立审查委员会（BIRC）评估的客观缓解率。次要终点包括研究者评估的客观缓解率；BIRC和研究者评估的疾病控制率、无进展生存期、反应时间和反应持续时间；总生存期；安全。

137名患者被随机分配接受sac-TMT（n=91）或多西他赛（n=46）治疗。在疗效数据截止时（2024年12月31日），中位随访时间为12.2个月。BIRC评估的客观缓解率在sac-TMT组（45%（41/91））和多西他赛组（16%（7/45））中显著较高，差异为29%（95%置信区间（CI）为15%至43%；单侧P<0.001）。经BIRC评估，囊性TMT的中位无进展生存期长于多西他赛（6.9 v 2.8个月；风险比0.30，95%CI 0.20至0.46；单侧P<0.001），研究者分析亦是如此（7.9 v 2.8个月中位；风险比0.23，0.15至0.36；单侧P<0.001）。囊性TMT的12个月总生存率为73%，多西他赛为54%（风险比0.49，0.27至0.88；单侧P=0.007）。使用保秩结构失效时间模型调整交叉后，sac-TMT也显示出总体生存率的提高（风险比0.36，0.20至0.66）。囊性TMT的≥3级治疗相关不良事件发生率低于多西他赛（56%对72%），没有发现新的安全信号。

研究结果表明，与多西他赛相比，Sac-TMT在客观反应率、无进展生存率和总生存率方面显示出统计学意义和临床意义的改善，在EGFR突变的局部晚期或转移性NSCLC患者中具有可控的安全性。

附：英文原文

Title: Sacituzumab tirumotecan versus docetaxel for previously treated EGFR-mutated advanced non-small cell lung cancer: multicentre, open label, randomised controlled trial

Author: Wenfeng Fang, Xingya Li, Qiming Wang, Xiangjiao Meng, Wei Zheng, Longhua Sun, Wenxiu Yao, Wu Zhuang, Yun Fan, Minglei Zhuo, Yongzhong Luo, Zhiye Zhang, Xia Song, Runxiang Yang, Jiacheng Yang, Xiaoping Jin, Yina Diao, Junyou Ge, Li Zhang

Issue&Volume: 2025/06/05

Abstract:

Objective To compare the efficacy and safety of sacituzumab tirumotecan (sac-TMT) with docetaxel in patients with locally advanced or metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.

Design Multicentre, open label, randomised controlled trial.

Setting 48 centres in China, 1 September 2023 to 31 December 2024.

Participants 137 adults (aged 18-75 years) with EGFR-mutated advanced or metastatic NSCLC after previous treatment failure with EGFR-tyrosine kinase inhibitors and platinum based chemotherapy.

Intervention Patients were randomly assigned (2:1) to receive sac-TMT (5 mg/kg) on days 1 and 15 of each four week cycle, or docetaxel (75 mg/m2) on day 1 of each three week cycle. Patients in the docetaxel group were permitted to crossover to sac-TMT treatment on disease progression.

Main outcome measures The primary endpoint was objective response rate as assessed by a blinded independent review committee (BIRC). The secondary endpoints included objective response rate assessed by the investigator; disease control rate, progression-free survival, time to response, and duration of response assessed by BIRC and the investigator; overall survival; and safety.

Results 137 patients were randomised to receive sac-TMT (n=91) or docetaxel (n=46). Median follow-up was 12.2 months at the data cut-off for efficacy (31 December 2024). BIRC assessed objective response rate was significantly higher in the sac-TMT group (45% (41/91)) v docetaxel (16% (7/45)), with a difference of 29% (95% confidence interval (CI) 15% to 43%; one sided P<0.001). Median progression-free survival was longer with sac-TMT than with docetaxel assessed by BIRC (6.9 v 2.8 months; hazard ratio 0.30, 95% CI 0.20 to 0.46; one sided P<0.001) and the investigator (7.9 v 2.8 months; hazard ratio 0.23, 0.15 to 0.36; one sided P<0.001). The 12 month overall survival rate was 73% with sac-TMT and 54% with docetaxel (hazard ratio 0.49, 0.27 to 0.88; one sided P=0.007). After adjustment for crossover using the rank-preserving structural failure time model, sac-TMT also showed improved overall survival (hazard ratio 0.36, 0.20 to 0.66). Grade ≥3 treatment related adverse events were less frequent with sac-TMT than with docetaxel (56% v 72%), with no new safety signals identified.

Conclusions Sac-TMT showed statistically significant and clinically meaningful improvements in objective response rate, progression-free survival, and overall survival compared with docetaxel, with a manageable safety profile in patients with EGFR-mutated locally advanced or metastatic NSCLC.

DOI: 10.1136/bmj-2025-085680

Source: https://www.bmj.com/content/389/bmj-2025-085680