Phase 3 study findings show that paclitaxel combined carboplatin stands up to the combination of paclitaxel and ifosfamide for the treatment of patients with uterine carcinosarcoma.
The combination of paclitaxel and carboplatin (PC) resulted in longer progression–free survival (PFS) and showed noninferiority overall survival result compared with paclitaxel and ifosfamide (PI) in patients with uterine carcinosarcoma (UCS), according to findings from the phase 3 NRG Oncology.1,2
For patients with UCS, there remain limitations with PI treatment because of its difficult administration to patients. Patients who receive PI also require growth factor support and have a higher risk for central neurologic toxicity. To potentially offer a new option for this patient population. the primary goal of the open-label, phase 3 NRG Oncology GOG 0261 study (NCT00954174) was to evaluate whether PC was noninferior to PI in terms of survival. The primary end point was OS, and the secondary end point was PFS.
The study enrolled 536 patients with UCS and 101 patients with ovarian carcinosarcoma (OCS). Results among the UCS patient population showed the median OS for patients treated with PC was 37 months vs patients treated with PI (HR, 0.87; 90% CI, 0.70 -1.075; P <.01 for noninferiority, P >.1 for superiority). The median PFS for this group was 16 months vs 12 months (HR, 0.73; P ≤.01 for noninferiority, P <.01 for superiority), respectively. In the OCS patient population, patients treated with PC saw a median OS of 30 months versus 25 months in patients treated with PI. The PFS in these patients was 15 months compared to 10 months, respectively. It Is important to note that researchers found these data in the OCS population were not statistically significant.1
“Women with uterine or ovarian carcinosarcomas typically present with this very aggressive disease at a late stage and tend to have a poor prognosis,” said Matthew A. Powell, MD, in a press release. “The current evidence-based standard of care is combined paclitaxel and ifosfamide, however, this treatment comes with several limitations and it was imperative to find an effective treatment alternative for women with this diagnosis.”
Of the 536 patients with UCS, 449 were eligible for the trial. Eligible patients were randomly assigned to PC (n = 228) or PI (n = 221) treatment. Treatment was administered intravenously in 3-week cycles lasting 6-10 cycles. Stratification by stage of disease showed that 40% were in stage I, 6% were in stage II, 31% were in stage III, 15% were in stage IV, and 8% had recurrent disease.
Of the 101 patients with OCS, 90 were eligible. Of these 90 patients, 44 were randomly assigned to PC and 46 were randomly assigned to PI.2
“The combination of paclitaxel and carboplatin has been tested in smaller studies and has safely shown activity for patients. NRG-GOG 0261 successfully concluded that this regimen is an effective and well tolerated treatment option for women with uterine carcinosarcoma,” added Powell, of Washington University School of Medicine, St. Louis, and the lead author on the study.
Based on the study findings, the investigators concluded that PC should be considered standard treatment for patients with UCS.
1. Powell MA, Filiaci VL, Hensley ML, et al. Randomized phase 3 trial of paclitaxel and carboplatin versus paclitaxel and ifosfamide in patients with carcinosarcoma of the uterus or ovary: an NRG oncology trial. Published online ahead of print. 2022. J Clin Oncol. doi:10.1200/JCO.21.02050
2. Paclitaxel and Carboplatin or Ifosfamide in Treating Patients With Newly Diagnosed, Persistent or Recurrent Uterine, Ovarian, Fallopian Tube, or Peritoneal Cavity Cancer. ClinicalTrials.gov. Updated September 30, 2021. Accessed January 13, 2022. https://bit.ly/3rhGYb8