转移性结直肠癌一线伊立替康的性别相关生存获益。III 期试验（XELAVIRI 研究，AIO-KRK-0110）的亚组分析。
Gender-dependent survival benefit from first-line irinotecan in metastatic colorectal cancer. Subgroup analysis of a phase III trial (XELAVIRI-study, AIO-KRK-0110).
机构信息
Department of Medicine III, University Hospital, LMU Munich, München, Germany; German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany; Medical Department, Division of Oncology and Hematology, Charité Universitaetsmedizin Berlin, Berlin, Germany.
出版信息
Eur J Cancer. 2021 Apr;147:128-139. doi: 10.1016/j.ejca.2021.01.025. Epub 2021 Feb 27.
BACKGROUND
XELAVIRI compared sequential (Arm A) versus initial (Arm B) irinotecan in combination with fluoropyrimidine plus bevacizumab in patients with metastatic colorectal cancer, trial identification: NCT01249638. In the full analysis set of the study, non-inferiority of time to failure of strategy (TFS) was not shown. The present analysis was performed to evaluate the effect of gender on treatment outcome and tolerability.
METHODS
The study end-points overall response rate (ORR), progression-free survival (PFS), TFS and overall survival (OS) were evaluated in female versus male patients and in molecular subgroups (i.e. RAS mutational status). Interaction of treatment and gender was tested by likelihood ratio tests.
RESULTS
In total, 281 male and 140 female patients (n = 421) were evaluated. Among the male patients, the ORR was 33.6% without and 58.3% with initial irinotecan (P < 0.001). PFS (hazard ratio [HR] 0.54; 95% confidence interval [CI] 0.42-0.69; P < 0.001) and OS (HR 0.63; 95% CI 0.47-0.85; P = 0.002) were also significantly better with initial irinotecan. Among the female patients, the ORR was 42.7% in Arm A and 43.1% in Arm B, PFS was similar (HR 1.09; 95% CI 0.76-1.55; P = 0.649) without and with initial irinotecan. A strong trend for inferior outcome with regard to OS with initial irinotecan was observed (HR 1.46; 95% CI 0.95-2.24; P = 0.081) and the trend reached significance in the multivariate analysis (HR 1.78; 95% CI 1.08-2.95; P = 0.02). Formal interaction of treatment and gender was observed for ORR (P = 0.018), PFS (P = 0.002) and OS (P = 0.001). Treatment-related adverse events were not significantly different between male and female patients.
CONCLUSIONS
The present analysis suggests that gender interacts with efficacy of initial irinotecan when used in combination with fluoropyrimidines and bevacizumab. Although male patients derived a significant and clinically meaningful benefit from initial combination chemotherapy, this was not observed in female patients.
背景
XELAVIRI 比较了转移性结直肠癌患者中先后（Arm A）与初始（Arm B）给予伊立替康联合氟嘧啶和贝伐珠单抗的疗效，试验识别号：NCT01249638。在该研究的全分析集，策略无失败时间（TFS）的非劣效性未得到证实。本分析旨在评估性别对治疗结局和耐受性的影响。
方法
本研究的终点包括总缓解率（ORR）、无进展生存期（PFS）、TFS 和总生存期（OS），在女性与男性患者和分子亚组（即 RAS 突变状态）中进行了评估。采用似然比检验检验治疗与性别之间的相互作用。
结果
共纳入 281 名男性和 140 名女性患者（n=421）。在男性患者中，ORR 分别为先后给予伊立替康无和有（58.3%）（P<0.001）。PFS（风险比 [HR] 0.54；95%置信区间 [CI] 0.42-0.69；P<0.001）和 OS（HR 0.63；95% CI 0.47-0.85；P=0.002）也显著改善。在女性患者中，Arm A 和 Arm B 的 ORR 分别为 42.7%和 43.1%，无和有初始伊立替康的 PFS 相似（HR 1.09；95% CI 0.76-1.55；P=0.649）。观察到 OS 结果有下降趋势，有初始伊立替康治疗的患者（HR 1.46；95% CI 0.95-2.24；P=0.081），且这种趋势在多变量分析中具有显著性（HR 1.78；95% CI 1.08-2.95；P=0.02）。ORR（P=0.018）、PFS（P=0.002）和 OS（P=0.001）观察到治疗与性别之间存在交互作用。男性和女性患者之间的治疗相关不良事件无显著差异。
结论
本分析表明，当氟嘧啶和贝伐珠单抗联合使用时，性别与初始伊立替康的疗效相互作用。虽然男性患者从初始联合化疗中获得了显著且有临床意义的获益，但在女性患者中未观察到。
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