Department of Obstetrics and Gynecology, University Hospitals Leuven, Leuven Cancer Institute, Leuven, Belgium; Department of Oncology, KU Leuven, Gynaecological Oncology, University Hospitals Leuven, Leuven, Belgium.
Division of Medical Oncology & Hematology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Gynecol Oncol. 2023 Nov;178:110-118. doi: 10.1016/j.ygyno.2023.09.013. Epub 2023 Oct 14.
This phase 2 study investigated sapanisertib (selective dual inhibitor of mTORC1/2) alone, or in combination with paclitaxel or TAK-117 (a selective small molecule inhibitor of PI3K), versus paclitaxel alone in advanced, recurrent, or persistent endometrial cancer.
Patients with histologic diagnosis of endometrial cancer (1-2 prior regimens) were randomized to 28-day cycles on four treatment arms: 1) weekly paclitaxel 80 mg/m (days 1, 8, and 15); 2) weekly paclitaxel 80 mg/m + oral sapanisertib 4 mg on days 2-4, 9-11, 16-18, and 23-25; 3) weekly sapanisertib 30 mg, or 4) sapanisertib 4 mg + TAK-117 200 mg on days 1-3, 8-10, 15-17, and 22-24.
Of 241 patients randomized, 234 received treatment (paclitaxel, n = 87 [3 ongoing]; paclitaxel+sapanisertib, n = 86 [3 ongoing]; sapanisertib, n = 41; sapanisertib+TAK-117, n = 20). The sapanisertib and sapanisertib+TAK-117 arms were closed to enrollment after futility analyses. After a median follow-up of 14.4 (paclitaxel) versus 17.2 (paclitaxel+sapanisertib) months, median progression-free survival (PFS; primary endpoint) was 3.7 versus 5.6 months (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.58-1.15; p = 0.139); in patients with endometrioid histology (n = 116), median PFS was 3.3 versus 5.7 months (HR 0.66; 95% CI 0.43-1.03). Grade ≥ 3 treatment-emergent adverse event rates were 54.0% with paclitaxel versus 89.5% paclitaxel+sapanisertib.
Our findings support inclusion of chemotherapy combinations with investigational agents for advanced or metastatic disease. The primary endpoint was not met and toxicity was manageable.
ClinicalTrials.gov number, NCT02725268.
本Ⅱ期研究旨在评估 sapaniertib（mTORC1/2 选择性双重抑制剂）单药治疗，或与紫杉醇或 TAK-117（一种选择性的 PI3K 小分子抑制剂）联合治疗，与紫杉醇单药治疗在晚期、复发性或持续性子宫内膜癌中的疗效。
组织学诊断为子宫内膜癌的患者（既往接受过 1-2 种方案）被随机分配至 4 个治疗组，接受 28 天周期治疗：1）每周紫杉醇 80mg/m2（第 1、8 和 15 天）；2）每周紫杉醇 80mg/m2+口服 sapaniertib 4mg 第 2-4、9-11、16-18 和 23-25 天；3）每周 sapaniertib 30mg，或 4）sapaniertib 4mg+TAK-117 200mg 第 1-3、8-10、15-17 和 22-24 天。
在 241 例随机患者中，234 例接受了治疗（紫杉醇，n=87 [3 例仍在进行中]；紫杉醇+sapanisertib，n=86 [3 例仍在进行中]；sapanisertib，n=41；sapanisertib+TAK-117，n=20）。在无效分析后，sapanisertib 和 sapanisertib+TAK-117 臂被关闭入组。中位随访 14.4 个月（紫杉醇）与 17.2 个月（紫杉醇+sapanisertib）后，中位无进展生存期（PFS；主要终点）分别为 3.7 个月与 5.6 个月（风险比[HR]0.82；95%置信区间[CI]0.58-1.15；p=0.139）；在子宫内膜样组织学患者（n=116）中，中位 PFS 分别为 3.3 个月与 5.7 个月（HR 0.66；95%CI 0.43-1.03）。紫杉醇组治疗相关不良事件发生率为 54.0%，紫杉醇+sapanisertib 组为 89.5%。
我们的研究结果支持在晚期或转移性疾病中加入化疗联合新型药物治疗。主要终点未达到，毒性可管理。
ClinicalTrials.gov 编号，NCT02725268。
