Abstract：
BACKGROUND: MAGNITUDE (NCT03748641) demonstrated favourable outcomes with niraparib plus abiraterone acetate plus prednisone (+AAP) versus placebo+AAP in patients with BRCA1/2-altered metastatic castration-resistant prostate cancer (mCRPC). Imbalances in prognostic variables were reported between arms, which impacts estimation of both the clinical benefit and cost‑effectiveness of niraparib+AAP for healthcare systems. A pre-specified multivariable analysis (MVA) demonstrated improved overall survival (OS) with niraparib+AAP. Here, we used an inverse probability of treatment weighting (IPTW) model to adjust for covariate imbalances and assess time-to-event outcomes.
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).
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).
摘要：
背景：MAGNITUDE（NCT03748641）在BRCA1/2改变的转移性去势抵抗性前列腺癌（mCRPC）患者中，尼拉帕尼布联合醋酸阿比特龙联合强的松（AAP）与安慰剂联合AAP相比，显示出良好的预后。两组之间报告了预后变量的不平衡，这影响了尼拉帕尼+AAP用于医疗保健系统的临床效益和成本效益的估计。预先指定的多变量分析（MVA）表明尼拉帕尼+AAP改善了总生存期（OS）。这里,我们使用治疗加权逆概率(IPTW)模型来校正协变量失衡并评估事件发生时间结局.
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）。
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）。
