A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695).
A Randomized Phase II Study of Coexpression Extrapolation (COXEN) with Neoadjuvant Chemotherapy for Bladder Cancer (SWOG S1314; NCT02177695).
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对膀胱癌的新辅助化疗的共表达外推（Coxen）的随机II期研究（SWOG S1314； NCT02177695）。
DOI：
10.1158/1078-0432.ccr-20-2409
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发表时间：
2021-05-01
期刊：
影响因子：
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通讯作者：
Thompson IM Jr
中科院分区：
文献类型：
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作者：
Flaig TW;Tangen CM;Daneshmand S;Alva A;Lerner SP;Lucia MS;McConkey DJ;Theodorescu D;Goldkorn A;Milowsky MI;Bangs R;MacVicar GR;Bastos BR;Fowles JS;Gustafson DL;Plets M;Thompson IM Jr
剂量密集的甲氨蝶呤-长春碱-阿霉素-顺铂（ddMVAC）和吉西他滨-顺铂（GC）是肌层浸润性膀胱癌（BC）接受的新辅助治疗方案。本研究的目的是验证来自共表达外推（COXEN）算法生成的基因表达模型（GEM）的评分作为接受根治性膀胱癌患者的生物标志物。合格性包括cT 2-T4 a N 0 M0、尿路上皮BC、≥ 5 mm的活瘤、顺铂合格，并计划进行化疗; 237例患者随机分配至ddMVAC组（每14天给药一次，共4个周期）和GC组（每21天给药一次，共4个周期）。主要目的是评估预先规定的二分治疗特异性COXEN评分，以预测手术时的pT 0率或≤ pT 1（降级）。在167例可评价患者中，GC治疗患者的pT 0与GC GEM评分的比值比为2.63（p=0.10; 95% CI [0.82，8.36]）;对于ddMVAC治疗的ddMVAC COXEN GEM评分，OR为1.12（p=0.82，95% CI [0.42，2.95]）。将GC GEM评分应用于合并组（GC和ddMVAC），以进行降级，OR为2.33（p=0.02; 95% CI [1.11，4.89]）。在对合格患者（n=227）进行的意向治疗分析中，ddMVAC和GC的pT 0率分别为28%和30%（p = 0.75）;降级率分别为47%和40%（p = 0.27）。治疗特异性COXEN评分不能显著预测个体化疗治疗的反应。在合并组中，COXEN GEM GC评分与分期下调显著相关。计划开发其他生物标志物。
Dose-dense Methotrexate-Vinblastine-Adriamycin-Cisplatin (ddMVAC) and Gemcitabine-Cisplatin (GC) are accepted neoadjuvant regimens for muscle-invasive bladder cancer (BC). The aim of this study was to validate the score from a Coexpression extrapolation (COXEN) algorithm-generated gene expression model (GEM) as a biomarker in patients undergoing radical cystectomy. Eligibility included cT2-T4a N0 M0, urothelial BC, ≥ 5 mm of viable tumor, cisplatin eligible, with plan for cystectomy; 237 patients were randomized between ddMVAC, given every 14 days for 4 cycles, and GC, given every 21 days for 4 cycles. The primary objective assessed pre-specified dichotomous treatment specific COXEN score as predictive of pT0 rate or ≤ pT1 (downstaging) at surgery. Among 167 evaluable patients, the odds ratio for pT0 with the GC GEM score in GC-treated patients was 2.63 (p=0.10; 95% CI [0.82,8.36]); for the ddMVAC COXEN GEM score with ddMVAC treatment, the OR was 1.12 (p=0.82, 95% CI [0.42, 2.95]). The GC GEM score was applied to pooled arms (GC and ddMVAC) for downstaging with an OR of 2.33 (p=0.02; 95% CI [1.11, 4.89]). In an intention to treat analysis of eligible patients (n=227), pT0 rates for ddMVAC and GC were 28% and 30% (p = 0.75); downstaging was 47% and 40% (p = 0.27), respectively. Treatment-specific COXEN scores were not significantly predictive for response to individual chemotherapy treatment. The COXEN GEM GC score was significantly associated with downstaging in the pooled arms. Additional biomarker development is planned.