曲平(T)联合顺铂放化疗（CRT）治疗局部晚期宫颈癌和阴道癌：NRG-GY006 III期随机试验结果

IF 4.5 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-03-17 DOI:10.1016/j.ygyno.2025.03.007

Charles A. Leath III , Wei Deng , Loren K. Mell , Debra L. Richardson , Joan L. Walker , Laura L. Holman , Jayanthi S. Lea , Sudha R. Amarnath , Luis Javier Santos-Reyes , Rebecca C. Arend , Jyoti Mayadev , Naresh Jegadeesh , Paul DiSilvestro , Hye Sook Chon , Sharad A. Ghamande , Lei Gao , Kevin Albuquerque , Junzo P. Chino , Eric Donnelly , Jonathan M. Feddock , Bradley J. Monk

{"title":"曲平(T)联合顺铂放化疗（CRT）治疗局部晚期宫颈癌和阴道癌：NRG-GY006 III期随机试验结果","authors":"Charles A. Leath III , Wei Deng , Loren K. Mell , Debra L. Richardson , Joan L. Walker , Laura L. Holman , Jayanthi S. Lea , Sudha R. Amarnath , Luis Javier Santos-Reyes , Rebecca C. Arend , Jyoti Mayadev , Naresh Jegadeesh , Paul DiSilvestro , Hye Sook Chon , Sharad A. Ghamande , Lei Gao , Kevin Albuquerque , Junzo P. Chino , Eric Donnelly , Jonathan M. Feddock , Bradley J. Monk","doi":"10.1016/j.ygyno.2025.03.007","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Findings</h3><div>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).</div></div><div><h3>Interpretation</h3><div>Triapine added to CRT did not improve OS.</div></div>","PeriodicalId":12853,"journal":{"name":"Gynecologic oncology","volume":"195 ","pages":"Pages 122-133"},"PeriodicalIF":4.5000,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial\",\"authors\":\"Charles A. Leath III , Wei Deng , Loren K. Mell , Debra L. Richardson , Joan L. Walker , Laura L. Holman , Jayanthi S. Lea , Sudha R. Amarnath , Luis Javier Santos-Reyes , Rebecca C. Arend , Jyoti Mayadev , Naresh Jegadeesh , Paul DiSilvestro , Hye Sook Chon , Sharad A. Ghamande , Lei Gao , Kevin Albuquerque , Junzo P. Chino , Eric Donnelly , Jonathan M. Feddock , Bradley J. Monk\",\"doi\":\"10.1016/j.ygyno.2025.03.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Findings</h3><div>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).</div></div><div><h3>Interpretation</h3><div>Triapine added to CRT did not improve OS.</div></div>\",\"PeriodicalId\":12853,\"journal\":{\"name\":\"Gynecologic oncology\",\"volume\":\"195 \",\"pages\":\"Pages 122-133\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-03-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gynecologic oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0090825825000769\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gynecologic oncology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0090825825000769","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

背景：以顺铂为基础的放化疗（CRT）加近距离放疗是局部晚期宫颈癌（LACC）的标准治疗方案。核糖核苷酸还原酶（RNR）的内在过表达可能促进CRT损伤的DNA修复。我们报告了在CRT中加入RNR抑制剂曲平(T)的结果。方法snrg - gy006是一项开放标签随机III期临床试验。FIGO 2009纳入无主动脉旁淋巴结受累的LACC （IB2、II、IIIB或IVA期）或II- iv期阴道癌。随机分配到CRT或结合每周三次的T （CRT + T）。放疗包括三维适形（3DCRT）或图像引导强度调节RT (IG-IMRT)，随后进行腔内近距离放疗。主要终点为总生存期（OS）。无进展生存期（PFS）是次要的。探索性终点包括治疗后PET/CT成像的完全代谢缓解率以及3DCRT与IG-IMRT的毒性和结果比较。结果：450例患者随机纳入，其中448例符合条件（CRT组224例，CRT + T组224例），中位年龄47岁（23-85岁）。多数为宫颈癌（93.3%），组织学为鳞状（82%）。52%为FIGO II期疾病。种族/民族分布包括非西班牙裔白人（53.8%）、黑人（15.2%）和西班牙裔/拉丁裔（22.5%）。随机分组时，74.3%的患者计划IG-IMRT， 98.2%的患者计划HDR近距离放疗。3-5级毒性无差异：CRT: 52%， CRT + T: 49%， CRT + T组有2个G5级毒性（心脏骤停和酸中毒）。患者中位随访时间为28个月（IQR 15-45）。死亡的HR为1.018 (95% CI 0.634-1.635)，进展的HR为1.021 （95% CI 0.694-1.501）。说明：曲平对CRT治疗无明显改善作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy