Washington University School of Medicine, St Louis, MO.
NRG Oncology, Clinical Trial Development Division, Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY.
J Clin Oncol. 2022 Mar 20;40(9):968-977. doi: 10.1200/JCO.21.02050. Epub 2022 Jan 10.
This phase III randomized trial (NCT00954174) tested the null hypothesis that paclitaxel and carboplatin (PC) is inferior to paclitaxel and ifosfamide (PI) for treating uterine carcinosarcoma (UCS).
Adults with chemotherapy-naïve UCS or ovarian carcinosarcoma (OCS) were randomly assigned to PC or PI with 3-week cycles for 6-10 cycles. With 264 events in patients with UCS, the power for an overall survival (OS) hybrid noninferiority design was 80% for a null hazard ratio (HR) of 1.2 against a 13% greater death rate on PI with a type I error of 5% for a one-tailed test.
The study enrolled 536 patients with UCS and 101 patients with OCS, with 449 and 90 eligible, respectively. Primary analysis was on patients with UCS, distributed as follows: 40% stage I, 6% stage II, 31% stage III, 15% stage IV, and 8% recurrent. Among eligible patients with UCS, PC was assigned to 228 and PI to 221. PC was not inferior to PI. The median OS was 37 versus 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; < .01 for noninferiority, > .1 for superiority). The median progression-free survival was 16 versus 12 months (HR = 0.73; = < 0.01 for noninferiority, < .01 for superiority). Toxicities were similar, except that more patients in the PC arm had hematologic toxicity and more patients in the PI arm had confusion and genitourinary hemorrhage. Among 90 eligible patients with OCS, those in the PC arm had longer OS (30 25 months) and progression-free survival (15 10 months) than those in the PI arm, but with limited precision, these differences were not statistically significant.
PC was not inferior to the active regimen PI and should be standard treatment for UCS.
本 III 期随机试验（NCT00954174）检验了紫杉醇联合卡铂（PC）劣于紫杉醇联合异环磷酰胺（PI）治疗子宫癌肉瘤（UCS）的无效假设。
新辅助化疗未接受的 UCS 或卵巢癌肉瘤（OCS）成年患者随机分配至 PC 或 PI 组，每 3 周治疗 6-10 个周期。UCS 患者有 264 个事件，在 HR 为 1.2（PI 组死亡率增加 13%）、单侧检验α值为 0.05 时，OS 混合非劣效设计的效能为 80%。
本研究纳入了 536 例 UCS 和 101 例 OCS 患者，分别有 449 例和 90 例符合条件。主要分析对象为 UCS 患者，分布如下：Ⅰ期 40%，Ⅱ期 6%，Ⅲ期 31%，Ⅳ期 15%，复发 8%。在符合条件的 UCS 患者中，PC 组 228 例，PI 组 221 例。PC 组未劣效于 PI 组。中位 OS 为 37 个月与 29 个月（HR=0.87；90%CI，0.70 至 1.075；P<.01 表示非劣效性，>0.1 表示优效性）。中位无进展生存期为 16 个月与 12 个月（HR=0.73；P<.01 表示非劣效性，<0.01 表示优效性）。毒性相似，PC 组血液学毒性更多，PI 组意识障碍和泌尿生殖系统出血更多。在 90 例符合条件的 OCS 患者中，PC 组 OS（30 25 个月）和无进展生存期（15 10 个月）均长于 PI 组，但因精度有限，这些差异无统计学意义。
PC 组与活性方案 PI 组相比无劣效性，应作为 UCS 的标准治疗方案。
