Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial
- PMID: 40101606
- PMCID: PMC12009185
- DOI: 10.1016/j.ygyno.2025.03.007
Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial
Abstract
Background: Cisplatin-based chemoradiation (CRT) plus brachytherapy for locally advanced cervical cancer (LACC) is standard. Intrinsic overexpression of ribonucleotide reductase (RNR) may enhance DNA damage repair from CRT. We report on outcomes of adding RNR inhibitor, triapine (T), to CRT.
Methods: NRG-GY006 is an open-label randomized phase III trial. FIGO 2009 LACC (stages IB2, II, IIIB or IVA) without para-aortic nodal involvement or stages II-IV vaginal cancer were eligible. Random assignment to CRT or in combination with thrice-weekly T (CRT + T) occurred. Radiation consisted of either 3D conformal (3DCRT) or image-guided intensity modulated RT (IG-IMRT) followed by intracavitary brachytherapy. Primary endpoint was overall survival (OS). Progression-free survival (PFS) was secondary. Exploratory endpoints included complete metabolic response rate on post treatment PET/CT imaging and comparative toxicity and outcomes for 3DCRT vs. IG-IMRT.
Findings: Four-hundred-fifty patients were randomized including 448 eligible (224 in CRT and 224 in CRT + T). Median age was 47 (range 23-85). The majority had cervical cancer (93.3 %) with squamous histology (82 %). 52 % had FIGO stage II disease. Racial/ethnic distribution included non-Hispanic white (53.8 %), black (15.2 %) and Hispanic/Latina (22.5 %). At randomization, IG-IMRT was planned in 74.3 % and HDR brachytherapy in 98.2 %. No differences in Grade 3-5 toxicities were observed: CRT: 52 % and CRT + T: 49 %, with two G5 toxicities (cardiac arrest and acidosis) in the CRT + T arm. The median patient follow-up was 28 months (IQR 15-45). HR for death was 1.018 (95 % CI 0.634-1.635) while HR for progression was 1.021 (95 % CI 0.694-1.501).
Interpretation: Triapine added to CRT did not improve OS.
Keywords: Chemoradiation; IMRT; Locally advanced cervical cancer; NCT02466971; Novel therapeutics.
Copyright © 2025 Elsevier Inc. All rights reserved.
Conflict of interest statement
Declaration of competing interest Dr. Charles Leath III received grants/contracts from National Institutes of Health – NCI UGI CA233330. He also received consulting fees from Seattle Genetics and Merck for cervical cancer consulting. Dr. Loren K. Mell received grants/contracts from Astra-Zeneca, Johnson & Johnson and Merck. He also received consulting fees from Pfizer and payment for expert testimony from Arnold Porter. Dr. Debra L. Richardson received grants/contracts from GSK. Consulting fees from Mersana and Targeted Oncology, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational event from Curio, Great Debates and Updates, research to Practice. She also received support for attending meetings and/or travel from GSK – ESGO registration. She participated on a Data Safety Monitoring Board and Advisory Board for Eisai, ProfoundBio, GSK, AstraZeneca, Immunogen and Daichi Sankyo. She held a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from BOD, NOCC and BOD SGO. Dr. Jayanthi S. Lea participated on a Data Safety Monitoring Board or Advisory Board for AstraZeneca and also held a leadership or fiduciary role on the American Board of Obstetrics & Gynecology. Dr. Rebecca Arend received consulting fees from Kiyatek, Inc. – consultant; MJH Healthcare Holdings, LLC – Advisory/consultant. She also received Honoraria from GOG Foundation, GSK, Curios Science LLC and VBL Therapeutics. She participated on Advisory Boards for GSK-2022, Merck – June 2022, Sutro – June 2022, Seagen Inc. – December 2021, AstraZeneca – October 2021 and Kiyatek – June 2021. Dr. Jyoti Mayadev served as Co-Chair of the Cervix Committee for NRG Oncology and NCI – RO1 co-investigator and R50 PI on NCI grants. She received consulting fees from AstraZeneca, Merck, Varian Medical Systems, Primmune and KORTUC. She also received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Merck, Varian Medical Systems and Primmune. She was also personally compensated for expert testimony. She receive support for attending meetings and/or travel from NRG Oncology. She is a member of the American Brachytherapy Society Board Member for 2023–2026. Dr. Sharad Ghamande received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from GSK. Dr. Junzo Chino received personal fees from Guidepoint and Personal Honoraria for Advisory Board from Merck. He received personal honoraria for chapter writing from GOG Foundation. He received personal fees for participation on a Data Safety Monitoring Board. He also serves as an Executive Board Member for the American Brachytherapy Society. Dr. Jessica Lowenstein's work is supported by grant # U24CA180803. Dr. Carol Aghajanian received clinical trial funding to her institute (MSKCC) from Abbvie – MSK PI, GOG3005, Artios Pharma – International Coordinating Investigator, ARTIST, AstraZeneca – MSK PI, SOLO1/GOG3004; National Coordinating Investigator & MSK PI, DO81RD00001; ENGOT – ov46, AGO-OVAR 23, GOG-3024; Clovis – MSK PI, ARIEL 2 & 3; Genentech/Roche – MSI PI, GOG3015 (IMagyn050). She served on a Virtual Advisory Board 6/30/21 (no consulting fee) for Blueprint Medicine; Global Cervical and Ovarian Cancer Virtual Advisory Board 7/10/23 for Merck; AZ EVOLVE DMC 4/26/23 – ongoing – Astra Zeneca; Future Clinical Strategies for Endometrial Cancer Virtual Advisory Board 3/13/24 – AstraZeneca; and RAMP 301 Steering Committee, 3/6/24 – ongoing. She also served on the Board of Directors (unpaid) for the GOG Foundation and the Board of Directors for the NRG Oncology. Dr. Bradley Monk received consulting fees from Acrivon, Adaptimune, Agenus, Akeso Bio, Amgen, Aravive, AstraZeneca, Bayer, Clovis, Easai, Elevar, EMD Merck, Genmab/Seagen, GOG Foundation, Gradalis, Heng Rui, ImmunoGen, Karyopharm, Iovance, Laekna, Macrogenics, Merck, Mersana, Myriad, Novartis, Novocure, OncoC4, Panavance, Pieris, Pfizer, Puma, Regeneron, Roche/Genentech, Sorrento, TESARO/GSK, US Oncology Research, VBL, Verastem and Zentalis. He also received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing of educational events from AstraZeneca, Easai, Myriad, Roche/Genentech and TESARO/GSK. All remaining co-authors have no conflicts of interest to declare.
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