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

Methods

Multicentre, open label, randomised controlled trial.

多中心、开放标签、随机对照试验。

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

在中国的48个中心，研究时间从2023年9月1日至2024年12月31日。

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.

137名年龄在18至75岁之间的成年患者，他们患有EGFR突变的晚期或转移性非小细胞肺癌（NSCLC），并且在之前的EGFR酪氨酸激酶抑制剂和基于铂的化疗治疗失败后。

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.

患者被随机分配（2:1），接受每四周一个周期的第1天和第15天静脉注射sac-TMT（5 mg/kg），或每三周一个周期的第1天静脉注射docetaxel（75 mg/m2）。

Patients in the docetaxel group were permitted to crossover to sac-TMT treatment on disease progression.

在docetaxel组的患者被允许在疾病进展时交叉接受sac-TMT治疗。

Methods

The primary endpoint was objective response rateas assessed by a blinded independent review committee (BIRC).

主要终点是由盲态独立评审委员会（BIRC）评估的客观缓解率。

The secondary endpoints included objective response rateassessed 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.

次要终点包括由研究者评估的客观缓解率；由BIRC和研究者评估的疾病控制率、无进展生存期、响应时间和响应持续时间；总生存期；以及安全性。

Results

137 patients were randomised to receive sac-TMT (n=91) or docetaxel (n=46).

137名患者被随机分配接受sac-TMT（n=91）或多西他赛（n=46）。

Median follow-up was 12.2 months at the data cut-off for efficacy (31 December 2024).

在2024年12月31日数据截止时，中位随访时间为12.2个月。

BIRC assessed objective response ratewas 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).

BIRC评估的客观缓解率在sac-TMT组显著高于多西他赛组（45%（41/91）vs 16%（7/45）），差异为29%（95%置信区间（CI）15%至43%；单侧P<0.001）。

Median progression-free survivalwas longer with sac-TMT than with docetaxel assessed by BIRC (6.9 v 2.8 months; hazard ratio0.30, 95% CI 0.20 to 0.46; one sided P<0.001) and the investigator (7.9 v 2.8 months; hazard ratio0.23, 0.15 to 0.36; one sided P<0.001).

BIRC评估的无进展生存期中位数在sac-TMT组比多西他赛组长（6.9个月vs 2.8个月；风险比0.30，95% CI 0.20至0.46；单侧P<0.001），研究者评估的无进展生存期中位数也更长（7.9个月vs 2.8个月；风险比0.23，0.15至0.36；单侧P<0.001）。

The 12 month overall survivalrate was 73% with sac-TMT and 54% with docetaxel (hazard ratio0.49, 0.27 to 0.88; one sided P=0.007).

使用sac-TMT治疗的12个月总生存率为73%，而使用多西他赛治疗的为54%（风险比0.49，95%置信区间0.27至0.88；单侧P=0.007）。

After adjustment for crossover using the rank-preserving structural failure time model, sac-TMT also showed improved overall survival(hazard ratio0.36, 0.20 to 0.66).

使用等级保持结构故障时间模型调整交叉后，sac-TMT显示出改善的总生存率（风险比0.36，95%置信区间0.20至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.

与多西他赛相比，使用sac-TMT的3级或更高级别的治疗相关不良事件发生率较低（56%对比72%），未发现新的安全信号。

Conclusions

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

在EGFR突变的局部晚期或转移性非小细胞肺癌患者中，与多西他赛相比，sac-TMT在客观缓解率、无进展生存期和总生存期方面显示出统计学上显著且具有临床意义的改善，且安全性可控。

trial_registration

ClinicalTrials.gov NCT05631262.

ClinicalTrials.gov NCT05631262。