This phase III study demonstrates that the combination of paclitaxel and carboplatin is non-inferior to the combination of paclitaxel and ifosfamide for the treatment of patients with uterine carcinosarcoma not previously treated with chemotherapy
This phase III randomized clinical trial aimed to determine paclitaxel and carboplatin (PC) can be considered non-inferior and potentially superior to paclitaxel and ifosfamide (PI) with respect to the duration of overall survival in the setting of uterine carcinosarcoma (UCS) treatment.
Adults with chemotherapy naive UCS or ovarian carcinosarcoma (OCS) were recruited for this study. These participants were randomly randomized to receive PC or PI in 3-week cycles for 6 to 10 cycles. With 264 events in patients with UCS, the power for an overall survival hybrid non-inferiority design was 80% for a null hazard ration of 1.2 against a 13% higher mortality rate on PI with a type I error of 5% for a single hypothesis test.
The present study enrolled 536 patients with UCS and 101 patients with OCS, which 449 and 90 eligible, respectively. Primary analysis was performed with UCS patients and resulted in 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 patients and PI to 221. The results showed that paclitaxel + carboplatin was non-inferior to paclitaxel + ifosfamide. Furthermore, the median overall survival was 37 vs 29 months (HR = 0.87; 90% CI, 0.70 to 1.075; P < 0.01 for non-inferiority, P > 0.1 for superiority). Median progression free survival was 16 vs12 months (HR=0.73; P=<0.01 for non-inferiority, P<0.01 for superiority). Toxicities was similar in both groups, except that more patients in the PC arm had hematological 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 greater overall survival and progression-free survival compared to those in the PI arm. With these results, we can conclude that the paclitaxel + carboplatin regimen was non-inferior to the active regimen paclitaxel + ifosfamide and should be considered as standard treatment for uterine carcinosarcoma. Reference:
Powell MA, et al., Randomized Phase III Trial of Paclitaxel and Carboplatin Versus Paclitaxel and Ifosfamide in Patients With Carcinosarcoma of the Uterus or Ovary: An NRG Oncology Trial. J Clin Oncol. 2022 Jan 10:JCO2102050. doi: 10.1200/JCO.21.02050. Epub ahead of print. PMID: 35007153.
