METHODS: IPTW analysis of time-to-event outcomes was conducted using data from patients with BRCA1/2-altered mCRPC (N = 225) in MAGNITUDE. Patients received niraparib+AAP or placebo+AAP. OS, radiographic progression-free survival, time to symptomatic progression, time to initiation of cytotoxic chemotherapy and time to prostate-specific antigen progression were assessed. Weighted Kaplan-Meier curves were generated for each endpoint, and adjusted hazard ratios (HR) were obtained from a weighted Cox model.
RESULTS: Improvements in survival outcomes were estimated for niraparib+AAP versus placebo+AAP: unadjusted median OS was 30.4 months versus 28.6 months, respectively (HR: 0.79; 95 % confidence interval [CI]: 0.55, 1.12; p = 0.183). Following IPTW, median OS increased to 34.1 months with niraparib+AAP versus a decrease to 27.4 with placebo (HR: 0.65; 95 % CI: 0.46, 0.93; p = 0.017). Similar improvements were observed for other time-to-event endpoints.
CONCLUSIONS: IPTW adjustment provided a more precise estimate of the clinical benefit of niraparib+AAP versus placebo+AAP in patients with BRCA1/2-altered mCRPC. Results were consistent with the pre-specified MVA, and further demonstrated the value of adjusting for baseline imbalances, particularly in smaller studies.
BACKGROUND: NCT03748641 (MAGNITUDE).
方法:使用MAGNITUDE中BRCA1/2改变的mCRPC患者(N=225)的数据,对事件发生时间结局进行IPTW分析。患者接受尼拉帕尼+AAP或安慰剂+AAP。操作系统,放射学无进展生存期,到症状进展的时间,评估了细胞毒性化疗开始的时间和前列腺特异性抗原进展的时间.为每个终点生成加权Kaplan-Meier曲线,和调整后的风险比(HR)从加权Cox模型获得。
结果:估计尼拉帕尼+AAP与安慰剂+AAP的生存结局改善:未校正的中位OS为30.4个月与28.6个月,分别(HR:0.79;95%置信区间[CI]:0.55,1.12;p=0.183)。在IPTW之后,尼拉帕利+AAP组的中位OS增加至34.1个月,而安慰剂组的中位OS降低至27.4个月(HR:0.65;95%CI:0.46,0.93;p=0.017).对于其他时间至事件终点观察到类似的改善。
结论:IPTW调整对尼拉帕尼+AAP与安慰剂+AAP在BRCA1/2改变的mCRPC患者中的临床益处提供了更精确的估计。结果与预先指定的MVA一致,并进一步证明了调整基线不平衡的价值,特别是在较小的研究中。
背景:NCT03748641(MAGNITUDE)。