三联吡啶胺（T）联合顺铂同步放化疗（CRT）治疗局部晚期宫颈癌和阴道癌：III期随机试验NRG-GY006的结果
Incorporation of triapine (T) to cisplatin chemoradiation (CRT) for locally advanced cervical and vaginal cancer: Results from NRG-GY006, a phase III randomized trial.
作者信息
Leath Charles A, Deng Wei, Mell Loren K, Richardson Debra L, Walker Joan L, Holman Laura L, Lea Jayanthi S, Amarnath Sudha R, Santos-Reyes Luis Javier, Arend Rebecca C, Mayadev Jyoti, Jegadeesh Naresh, DiSilvestro Paul, Chon Hye Sook, Ghamande Sharad A, Gao Lei, Albuquerque Kevin, Chino Junzo P, Donnelly Eric, Feddock Jonathan M, Lowenstein Jessica, Quick Allison M, Kunos Charles M, MacKay Helen, Aghajanian Carol, Monk Bradley J
机构信息
University of Alabama at Birmingham, O'Neal Comprehensive Cancer Center, Birmingham, AL, United States of America.
NRG Statistical Center, Roswell Park Cancer Institute, Buffalo, NY, United States of America.
出版信息
Gynecol Oncol. 2025 Apr;195:122-133. doi: 10.1016/j.ygyno.2025.03.007. Epub 2025 Mar 17.
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.
背景
基于顺铂的同步放化疗（CRT）联合近距离放射治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）的内在过表达可能增强CRT对DNA的损伤修复作用。我们报告了在CRT基础上加用RNR抑制剂曲阿普明（T）的治疗结果。
方法
NRG-GY006是一项开放标签的随机III期试验。符合条件的患者为2009年国际妇产科联盟（FIGO）分期的LACC（IB2、II、IIIB或IVA期）且无主动脉旁淋巴结受累，或II-IV期阴道癌患者。患者被随机分配接受CRT或CRT联合每周3次的T（CRT+T）治疗。放疗采用三维适形放疗（3DCRT）或图像引导调强放疗（IG-IMRT），随后进行腔内近距离放射治疗。主要终点是总生存期（OS）。无进展生存期（PFS）是次要终点。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的毒性和疗效对比。
结果
450例患者被随机分组，其中448例符合条件（CRT组224例，CRT+T组224例）。中位年龄为47岁（范围23-85岁）。大多数患者为宫颈癌（93.3%），组织学类型为鳞状细胞癌（82%）。52%的患者为FIGO II期疾病。种族/族裔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%的患者计划接受IG-IMRT，98.2%的患者计划接受高剂量率近距离放射治疗。未观察到3-5级毒性反应的差异：CRT组为52%，CRT+T组为49%，CRT+T组有2例5级毒性反应（心脏骤停和酸中毒）。患者的中位随访时间为28个月（四分位间距15-45个月）。死亡风险比（HR）为1.018（95%置信区间0.634-1.635），进展风险比为1.021（95%置信区间0.694-1.501）。
结论
在CRT基础上加用曲阿普明并未改善总生存期。
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