SCI

26 June 2024

Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study

(Journal of Clinical Oncology, IF: 42.1)

  • Luis G. Paz-Ares; Oscar Juan-Vidal; Giannis S. Mountzios; Enriqueta Felip; Niels Reinmuth; Filippo de Marinis; Nicolas Girard; Vipul M. Patel; Takayuki Takahama; Scott P. Owen; Douglas M. Reznick; Firas B. Badin; Irfan Cicin; Sabeen Mekan; Riddhi Patel; Eric Zhang; Divyadeep Karumanchi; and Marina Chiara Garassino

  • CORRESPONDENCE TO: lpazaresr@seom.org.

PURPOSE 目的

The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non–small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti–PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported.

这项开放标签III期EVOKE-01研究评估了转移性非小细胞肺癌（mNSCLC）中Sacituzumab Govitecan（SG）与标准治疗多西他赛的疗效，这些肺癌患者既往接受基于铂类的化疗、抗PD-（L）1治疗和基因组改变（AGA）靶向治疗后肿瘤有进展。本文报告了初步分析。

 

METHODS 方法

Patients were randomly assigned 1:1 (stratified by histology, best response to last anti–PD-(L)1–containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m2 intravenous infusion on day 1) in 21-day cycles. Primary end point was overall survival (OS). Key secondary end points were investigator assessed progression-free survival (PFS), objective response rate, patient reported symptom assessment, and safety.

患者按1:1（按组织学分层，最后一次抗PD-（L）1-方案的反应，以及是否接受AGA治疗）随机分为SG组（第1天和第8天静脉输注10 mg/kg）或多西他赛组（第1天静脉输注75 mg/m2），共21天为一周期。主要终点是总生存期（OS）。关键的次要终点是研究者评估的无进展生存期（PFS）、客观有效率、患者报告的症状评估和安全性。

 

RESULTS 结果

In the intention-to-treat population (SG, n = 299; docetaxel, n = 304), 55.4% had one previous line of therapy. Median follow-up was 12.7 months (range, 6.0-24.0). The primary end point was not met. There was a numerical OS improvement for SG versus docetaxel (median, 11.1 v 9.8 months; hazard ratio [HR], 0.84 [95% CI, 0.68 to 1.04]; one-sided P = .0534), consistent across squamous and nonsquamous histologies. Median PFS was 4.1 versus 3.9 months (HR, 0.92 [95% CI, 0.77 to 1.11]). An OS benefit was observed for SG (n = 192) versus docetaxel (n = 191) in mNSCLC nonresponsive to last anti–PD-(L)1–containing regimen (3.5-month median OS increase; HR, 0.75 [95% CI, 0.58 to 0.97]); this was consistent across histologies. Among patients receiving SG and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively; 1.4% and 1.0%, respectively, had TRAEs leading to death. 

在意向治疗人群（SG组 n = 299；多西他赛组 n = 304）中，55.4%的患者曾接受过既往治疗。中位随访时间为12.7个月（范围6.0-24.0）。主要终点目前尚未达到。与多西他赛相比，SG组患者的OS在数值上有改善（中位数为11.1个月对9.8个月；危险比[HR]为0.84[95%CI，0.68-1.04]；单侧P = 0.0534），这一结果在鳞状和非鳞状肺癌组织中一致。中位PFS为4.1个月与3.9个月（HR，0.92[95%CI，0.77-1.11]）。在对最后一次抗PD-（L）1方案治疗后无反应的mNSCLC中，观察到SG组（n = 192）与多西他赛组（n = 191）患者的OS获益（3.5个月的中位OS率增加；HR，0.75[95%CI，0.58至0.97]）；这在不同的肺癌病理类型中是一致的。在接受SG和多西他赛治疗的患者中，分别有6.8%和14.2%的患者因治疗相关不良事件（TRAE）而停药；1.4%和1.0%的患者因TRAE导致死亡。

 

CONCLUSION 结论

Although statistical significance was not met, OS numerically improved with SG versus docetaxel, which was consistent across histologies. Clinically meaningful improvement in OS was noted in mNSCLC nonresponsive to last anti–PD-(L)1– containing regimen. SG was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.

尽管没有达到统计学意义，但SG与多西他赛相比，OS在数值上有所改善，这在各病理学类型上是一致的。在对最后一次抗PD-（L）1的方案无反应的mNSCLC中，OS有临床意义的改善。SG组的患者对药物的耐受优于多西他赛，且与其已知的安全性一致，没有新的安全性信号。