Gemcitabine plus docetaxel is an effective treatment regimen for advanced soft tissue sarcomas (STSs). However, the prognosis for patients remains poor, and thus there is an urgent medical need for novel and effective therapies to improve long-term outcomes. The aim of the ANNOUNCE 2 trial was to explore the addition of olaratumab (O) to gemcitabine (G) and docetaxel (D) for advanced STS. Adults with unresectable locally advanced/metastatic STS, ≤2 prior lines of systemic therapy, and ECOG PS 0–1 were eligible. In Phase 2, patients were randomized 1:1 from two cohorts (O-naïve and O-pretreated) to 21-day cycles of olaratumab (20 mg/kg Cycle 1 and 15 mg/kg other cycles, Days 1 and 8), gemcitabine (900 mg/m2, Days 1 and 8), and docetaxel (75 mg/m2, Day 8). The primary objective was overall survival (OS) in the O-naïve population (α level = 0.20). Secondary endpoints included OS (O-pretreated), other efficacy parameters, patient-reported outcomes, safety, pharmacokinetics, and immunogenicity. A total of 167 and 89 patients were enrolled in the O-naïve and O-pretreated cohorts, respectively. Baseline patient characteristics were well balanced. No statistically significant difference in OS was observed between the investigational vs. control arm for either cohort (O-naïve cohort: HR = 0.95 (95% CI: 0.64−1.40),p= 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39−1.16),p= 0.15, median OS 19.8 vs. 17.3 months). Safety was manageable across treatment arms. There was no statistically significant difference in the primary endpoint of OS between the two arms in the O-naïve population, and therefore based on hierarchical evaluation no other outcomes in this study can be considered statistically significant. No new safety signals were observed.
吉西他滨联合多西他赛是治疗晚期软组织肉瘤的有效方案。然而患者预后仍然较差，因此迫切需要新型有效的疗法以改善长期结局。ANNOUNCE 2试验旨在探索在吉西他滨和多西他赛基础上联合奥拉单抗治疗晚期软组织肉瘤的疗效。研究纳入不可切除的局部晚期/转移性软组织肉瘤成人患者，既往接受≤2线全身治疗，ECOG PS评分为0-1分。在第二阶段，患者根据是否接受过奥拉单抗治疗分为两个队列（初治队列与经治队列），按1:1比例随机分配至21天治疗周期：奥拉单抗（第1周期20 mg/kg，后续周期15 mg/kg，第1、8天给药）、吉西他滨（900 mg/m²，第1、8天给药）和多西他赛（75 mg/m²，第8天给药）。主要研究终点为奥拉单抗初治人群的总生存期（α水平=0.20）。次要终点包括经治人群总生存期、其他疗效参数、患者报告结局、安全性、药代动力学和免疫原性。初治队列与经治队列分别入组167例和89例患者，基线特征均衡。两个队列中试验组与对照组的总生存期均未观察到统计学显著差异（初治队列：HR=0.95（95% CI：0.64-1.40），p=0.78，中位总生存期16.8个月 vs 18.0个月；经治队列：HR=0.67（95% CI：0.39-1.16），p=0.15，中位总生存期19.8个月 vs 17.3个月）。各治疗组安全性可控。由于奥拉单抗初治人群的主要终点总生存期未显示统计学显著差异，根据分层检验原则，本研究其他结局均不能视为具有统计学显著性。未观察到新的安全性信号。
肿瘤(癌症)患者之家