A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study Journal Article

  

Authors:	Bae-Jump, V. L.; Sill, M. W.; Gehrig, P. A.; Merker, J. D.; Corcoran, D. L.; Pfefferle, A. D.; Hayward, M. C.; Walker, J. L.; Hagemann, A. R.; Waggoner, S. E.; O'Cearbhaill, R. E.; McDonald, M. E.; Edelson, M. I.; DiSilvestro, P. A.; McNally, A. L.; Fleury, A.; Littell, R. D.; Ueland, F. R.; Lankes, H. A.; Aghajanian, C.
Article Title:	A randomized phase II/III study of paclitaxel/carboplatin/metformin versus paclitaxel/carboplatin/placebo as initial therapy for measurable stage III or IVA, stage IVB, or recurrent endometrial cancer: An NRG oncology/GOG study
Abstract:	Introduction: We evaluated the efficacy of the addition of the anti-diabetic drug metformin to standard-of-care paclitaxel and carboplatin (PC) in patients with advanced and recurrent endometrial cancer (EC). Methods: In this phase II/III trial, EC patients with chemotherapy-naïve stage III/IVA (with measurable disease) and stage IVB or recurrent (with or without measurable disease) disease were randomly assigned to PC/metformin (850 mg BID) versus PC/placebo. Metformin or placebo was continued as maintenance therapy after completion of PC until disease progression. The primary endpoint of phase II was progression-free survival (PFS). The primary endpoint of phase III was overall survival (OS). Secondary endpoints were objective response, duration of response, and toxicity. Results: From 3/17/2014 to 12/22/2017, 448 patients were randomized to phase II/III studies, and the data were frozen for interim analysis. The phase II study deemed metformin worthy of further investigation in the phase III study. The interim phase III analysis stopped accrual for futility on 2/1/2018. The addition of metformin to PC had a slightly higher hazard of death compared to the PC regimen (HR = 1.088; 90% CI 0.803 to 1.475), which was sufficient to close the study early. The PFS had (HR = 0.814; 90% CI 0.635 to 1.043). At a median follow-up of 10 months and 121 deaths, median OS was not determined and 28 months, on PC/placebo and PC/metformin, respectively. Conclusion: The hazard ratios for PFS and OS endpoints was not sufficiently decreased with the addition of metformin to PC to justify continuing the trial. © 2025 The Authors
Keywords:	adult; clinical article; controlled study; treatment response; aged; middle aged; overall survival; clinical trial; drug tolerability; cancer recurrence; placebo; cancer combination chemotherapy; cancer growth; drug efficacy; drug safety; paclitaxel; cancer staging; follow up; endometrial cancer; endometrium cancer; carboplatin; progression free survival; infection; multiple cycle treatment; phase 2 clinical trial; heart disease; kidney disease; randomized controlled trial; add on therapy; mental disease; skin disease; phase 3 clinical trial; eye disease; connective tissue disease; drug dose increase; neurologic disease; gastrointestinal disease; metformin; metabolic disorder; thorax disease; musculoskeletal disease; endocrine disease; immunopathology; polyp; injury; hematologic disease; vascular disease; respiratory tract disease; breast disease; cyst; lymphatic system disease; genital system disease; clinical outcome; ear disease; urinary tract disease; Common Terminology Criteria for Adverse Events; maintenance chemotherapy; benign neoplasm; mediastinum disease; nutritional disorder; inner ear disease; very elderly; human; female; article; infestation; mortality risk; malignant neoplasm
Journal Title:	Gynecologic Oncology
Volume:	195
ISSN:	0090-8258
Publisher:	Elsevier Inc.
Date Published:	2025-04-01
Start Page:	66
End Page:	74
Language:	English
DOI:	10.1016/j.ygyno.2025.03.003
PROVIDER:	scopus
PUBMED:	40056832
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85219669833&doi=10.1016%2fj.ygyno.2025.03.003&partnerID=40&md5=84ee89ac56c7c0c6491ffa33cbbc4da5
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/223753