January 11 2022
Results from the phase 3 NRG Oncology GOG 0261 clinical trial demonstrated that women with uterine carcinosarcoma (UCS) treated with a combination of paclitaxel and carboplatin exhibited longer progression-free survival and non-inferior duration of overall survival compared to women who were treated with a combination of paclitaxel and ifosfamide. These data provide significant evidence to consider paclitaxel and carboplatin the new standard of care for this patient population. These results were recently published in the Journal of Clinical Oncology.
“Women with uterine or ovarian carcinosarcomas typically present with this very aggressive disease at a late stage and tend to have a poor prognosis” stated Matthew A. Powell, MD of Washington University School of Medicine, St. Louis, and the Lead Author of the NRG-GOG 0261 manuscript. “The current evidence-based standard of care is treatment with 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.”
Although treatment with paclitaxel and ifosfamide has displayed improved survival outcomes for patients in previous clinical trials, this regimen has limitations due to its difficulty to administer to patients, its required use of growth factor support, and this greater risk for central neurologic toxicity.
“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 Dr. Powell.
NRG-GOG 0261 enrolled 449 eligible women with UCS and 90 with ovarian carcinosarcoma (OCS) and randomly assigned treatment of paclitaxel and carboplatin or paclitaxel and ifosfamide to trial participants. The primary aim of the trial was to test if the combination of paclitaxel and carboplatin was inferior to the combination of paclitaxel and ifosfamide in terms of overall survival for patients.
Analysis showed that paclitaxel and carboplatin was not inferior to paclitaxel and ifosfamide treatment. The median overall survival for women with UCS treated with paclitaxel and carboplatin was 37 months compared to 29 months for women treated with paclitaxel and ifosfamide. (Hazard Ratio [HR] = 0.87; 90% confidence interval [CI] = 0.70 – 1.075; P<0.01 for non-inferiority, P>0.1 for superiority). Median progression-free survival for patients with UCS was 16 months for patients treated with paclitaxel/carboplatin versus 12 months for patients treated with paclitaxel/ifosfamide. (HR = 0.73; P = < 0.01 for non-inferiority, P<0.01 for superiority). Toxicity rates on the treatment arms were similar. Differences were not statistically significant for patients with OCS, as the paclitaxel/carboplatin treatment had a median overall survival of 30 months compared to 25 months for paclitaxel/ifosfamide and median progression-free survival was 15 months for patients treated with paclitaxel/carboplatin compared to 10 months on patients treated with paclitaxel/ifosfamide.
This study was supported by 1 U10 CA180822 (NRG Oncology SDMC), UG1CA189867 (NCORP), U10CA180868 (NRG Operations), and U24CA186067 (NRG Specimen Bank) grants from the National Cancer Institute, part of the National Institutes of Health. The study was led by NRG Oncology and conducted by the NCI funded National Clinical Trials Network (NCTN).
Citation
Powell MA, Filiaci VL, Hensley ML, Huang HQ, Moore KN, Tewari KS, Copeland LJ, Secord AA, Mutch DG, Santin A, Warshal DP, Spirtos NM, DiSilvestro PA, Ioffe OB, Miller DS. 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.
About NRG Oncology
NRG Oncology conducts practice-changing, multi-institutional clinical and translational research to improve the lives of patients with cancer. Founded in 2012, NRG Oncology is a Pennsylvania-based nonprofit corporation that integrates the research of the legacy National Surgical Adjuvant Breast and Bowel Project (NSABP), Radiation Therapy Oncology Group (RTOG), and Gynecologic Oncology Group (GOG) programs. The research network seeks to carry out clinical trials with emphases on gender-specific malignancies, including gynecologic, breast, and prostate cancers, and on localized or locally advanced cancers of all types. NRG Oncology’s extensive research organization comprises multidisciplinary investigators, including medical oncologists, radiation oncologists, surgeons, physicists, pathologists, and statisticians, and encompasses more than 1,300 research sites located world-wide with predominance in the United States and Canada. NRG Oncology is supported primarily through grants from the National Cancer Institute (NCI) and is one of five research groups in the NCI’s National Clinical Trials Network.