Gordon Erlinda Maria, Chawla Sant P, Tellez Walter Andree, Younesi Elan, Thomas Sonu, Chua-Alcala Victoria S, Chomoyan Hripsime, Valencia Chrysler, Brigham Don Arlen, Moradkhani Ania, Quon Doris, Srikureja Amornchit, Wong Steven G, Tseng William, Federman Noah
Sarcoma Oncology Research Center, Santa Monica, CA 90403, USA.
Aveni Foundation, Santa Monica, CA 90403, USA.
Cancers (Basel). 2023 Jan 31;15(3):906. doi: 10.3390/cancers15030906.
This Phase 1/2 study is based on the hypothesis that immune checkpoint inhibitors are more effective when given earlier in the course of the disease for advanced soft tissue sarcoma.
Phase I endpoints-maximum tolerated dose in previously treated patients; Phase II endpoints-best response, progression free survival and overall survival and incidence of adverse events in previously untreated patients; Phase I treatments-escalating doses of trabectedin (1.0, 1.2, 1.5 mg/m) as continuous intravenous infusion over 24 h every 3 weeks, 1 mg/kg of ipilimumab given intravenously every 12 weeks, and 3 mg/kg of nivolumab given intravenously every 2 weeks; Phase II treatments-maximum tolerated dose of trabectedin and defined doses of ipilimumab and nivolumab.
Phase I ( = 9)-the maximum tolerated dose of trabectedin was 1.2 mg/m; Phase II ( = 79)-6 complete responses, 14 partial responses, 49 stable disease, 25.3% best response rate, 87.3% disease control rate; median progression-free survival, 6.7 months (CI 95%: 4.4-7.9), median overall survival, 24.6 months (CI 95%: 17.0-.); Grade 3/4 therapy-related adverse events ( = 92)-increased ALT (25%), fatigue (8.7%), increased AST (8.7%), decreased neutrophil count (5.4%) and anemia (4.6%).
SAINT is a safe and effective first-line treatment for advanced soft tissue sarcoma.
这项1/2期研究基于这样的假设，即对于晚期软组织肉瘤，免疫检查点抑制剂在疾病进程中更早给药时效果更佳。
I期终点——先前接受过治疗的患者的最大耐受剂量；II期终点——最佳反应、无进展生存期和总生存期，以及先前未接受过治疗的患者的不良事件发生率；I期治疗——曲贝替定剂量递增（1.0、1.2、1.5mg/m²），每3周连续静脉输注24小时，每12周静脉注射1mg/kg伊匹木单抗，每2周静脉注射3mg/kg纳武单抗；II期治疗——曲贝替定的最大耐受剂量以及确定剂量的伊匹木单抗和纳武单抗。
I期（n = 9）——曲贝替定的最大耐受剂量为1.2mg/m²；II期（n = 79）——6例完全缓解，14例部分缓解，49例病情稳定，最佳反应率25.3%，疾病控制率87.3%；中位无进展生存期6.7个月（95%CI：4.4 - 7.9），中位总生存期24.6个月（95%CI：17.0 - ）；3/4级治疗相关不良事件（n = 92）——谷丙转氨酶升高（25%）、疲劳（8.7%）、谷草转氨酶升高（8.7%）、中性粒细胞计数降低（5.4%）和贫血（4.6%）。
SAINT是晚期软组织肉瘤安全有效的一线治疗方法。
