■涉及多个治疗线的癌症试验大大增加了我们对治疗策略的理解。然而,即使这些研究的主要终点是无进展生存期(PFS),他们的统计分析通常分别关注每一行,或者不考虑重复的事件,因此缺少潜在的相关信息。因此,对治疗策略有效性的评估严重受损.
我们在ITACa(意大利晚期结直肠癌试验)随机试验中评估了贝伐单抗(B)用于一线或二线治疗转移性结直肠癌(mCRC)的潜在不同效果。ITACa试验包括两组:一线化疗(CT)B,然后是单独的二线CT,而根据KRAS状态,仅一线CT,然后是二线CTB或CTB西妥昔单抗。重复疾病进展的Cox模型,潜在选择偏差采用逆概率审查加权法进行调整。报告了PFS(主要终点)的危险比(HR)[95%置信区间(CI)]。
■B在两条线上的总体效果导致HR=0.80(95%CI0.68-0.95,p=0.008)。评估B在一线和二线的差异效应,与单用CT相比,在一线化疗(CT)中添加B可降低10%的风险(HR=0.90,95%CI0.72~1.12,p=0.340);与单用CT相比,在二线CT中添加B可降低36%的风险(HR=0.64,95%CI0.49~0.84,p=0.0011).
■我们的结果似乎表明,B与二线化疗联合使用时具有PFS优势,这可能有助于改善当前有关最佳序贯治疗策略的国际指南。
UNASSIGNED: Cancer trials involving multiple treatment lines substantially increase our understanding of therapeutic strategies. However, even when the primary end-point of these studies is progression-free survival (PFS), their statistical analysis usually focuses on each line separately, or does not consider repeated events, thus missing potentially relevant information. Consequently, the evaluation of the effectiveness of treatment strategies is highly impaired.
UNASSIGNED: We evaluated the potentially different effect of bevacizumab (B) administered for the first- or second-line treatment of metastatic colorectal cancer (mCRC) in the ITACa (Italian Trial in Advanced Colorectal Cancer) randomized trial. The ITACa trial consisted of two arms: first-line chemotherapy (CT)+B followed by second-line CT alone versus first-line CT alone followed by second-line CT+B or CT+B+cetuximab according to KRAS status. Cox models for repeated disease progression were performed, and potential selection bias was adjusted using the inverse probability of censoring weighting method. Hazard ratios (HR) [95% confidence interval (CI)] for PFS (primary endpoint) were reported.
UNASSIGNED: The overall effect of B across the two lines resulted in a HR = 0.80 (95% CI 0.68-0.95, p = 0.008). Evaluating the differential effect of B in first- and second-line, the addition of B to first-line chemotherapy (CT) produced a 10% risk reduction (HR = 0.90, 95% CI 0.72-1.12, p = 0.340) versus CT alone; B added to second-line CT produced a 36% risk reduction (HR = 0.64, 95% CI 0.49-0.84, p = 0.0011) versus CT alone.
UNASSIGNED: Our results seem to suggest that B confers a PFS advantage when administered in combination with second-line chemotherapy, which could help to improve current international guidelines on optimal sequential treatment strategies.