Attia Steven, Villalobos Victor, Hindi Nadia, Wagner Andrew J, Chmielowski Bartosz, Oakley Gerard J, Peterson Patrick M, Ceccarelli Matteo, Jones Robin L, Dickson Mark A
Mayo Clinic, Jacksonville, FL 32224, USA.
School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.
Cancers (Basel). 2023 Oct 6;15(19):4871. doi: 10.3390/cancers15194871.
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/m, Days 1 and 8), and docetaxel (75 mg/m, 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), = 0.78, median OS, 16.8 vs. 18.0 months; O-pretreated cohort: HR = 0.67 (95% CI: 0.39-1.16), = 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晚期软组织肉瘤（STS）的一种有效治疗方案。然而，患者的预后仍然很差，因此迫切需要新的有效疗法来改善长期疗效。ANNOUNCE 2试验的目的是探索在吉西他滨（G）和多西他赛（D）基础上加用奥拉单抗（O）治疗晚期STS。符合条件的患者为年龄≥18岁、不可切除的局部晚期/转移性STS、既往全身治疗线数≤2且东部肿瘤协作组（ECOG）体能状态（PS）为0 - 1的患者。在2期试验中，患者从两个队列（未使用过奥拉单抗和曾使用过奥拉单抗）按1:1随机分组，接受21天周期的治疗，具体为：奥拉单抗（第1周期20 mg/kg，其他周期15 mg/kg，第1天和第8天）、吉西他滨（900 mg/m²，第1天和第8天）和多西他赛（75 mg/m²，第8天）。主要终点是未使用过奥拉单抗人群的总生存期（OS）（α水平 = 0.20）。次要终点包括曾使用过奥拉单抗人群的OS、其他疗效参数、患者报告的结局、安全性、药代动力学和免疫原性。未使用过奥拉单抗队列和曾使用过奥拉单抗队列分别有167例和89例患者入组。基线患者特征均衡。两个队列的研究组与对照组之间在OS方面均未观察到统计学显著差异（未使用过奥拉单抗队列：风险比（HR）= 0.95（95%置信区间（CI）：0.64 - 1.40），P = 0.78，中位OS，16.8个月对18.0个月；曾使用过奥拉单抗队列：HR = 0.67（95% CI：0.39 - 1.16），P = 0.15，中位OS 19.8个月对17.3个月）。各治疗组的安全性均可管理。在未使用过奥拉单抗人群中，两组在主要终点OS方面无统计学显著差异，因此根据分层评估，本研究中的其他结局均不能认为具有统计学显著性。未观察到新的安全信号。
