Department of Medical Oncology, Institut Bergonié, Bordeaux, France.
University College London Cancer Institute, London, UK.
Eur J Cancer. 2024 Sep;209:114183. doi: 10.1016/j.ejca.2024.114183. Epub 2024 Jun 17.
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.
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.
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.
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.
NCT03748641 (MAGNITUDE).
MAGNITUDE（NCT03748641）研究表明，与安慰剂+AAP 相比，尼拉帕利+醋酸阿比特龙+泼尼松（+AAP）在 BRCA1/2 改变的转移性去势抵抗性前列腺癌（mCRPC）患者中具有更好的疗效。报告称，各治疗组之间存在预后变量的不平衡，这会影响对尼拉帕利+AAP 治疗方案的临床获益和成本效益的估计，对于医疗保健系统而言。一项预设的多变量分析（MVA）表明，尼拉帕利+AAP 可改善总生存期（OS）。在这里，我们使用逆概率治疗加权（IPTW）模型来调整协变量的不平衡，并评估时间事件结局。
使用 MAGNITUDE 中 BRCA1/2 改变的 mCRPC 患者（N=225）的数据进行时间事件结局的 IPTW 分析。患者接受尼拉帕利+AAP 或安慰剂+AAP 治疗。评估 OS、影像学无进展生存期、症状进展时间、细胞毒性化疗开始时间和前列腺特异性抗原进展时间。为每个终点生成加权 Kaplan-Meier 曲线，并从加权 Cox 模型获得调整后的危险比（HR）。
与安慰剂+AAP 相比，尼拉帕利+AAP 组的生存结局得到了改善：未经调整的中位 OS 分别为 30.4 个月和 28.6 个月（HR：0.79；95%置信区间[CI]：0.55，1.12；p=0.183）。在 IPTW 后，尼拉帕利+AAP 组的中位 OS 增加至 34.1 个月，而安慰剂组则降至 27.4 个月（HR：0.65；95%CI：0.46，0.93；p=0.017）。其他时间事件终点也观察到类似的改善。
IPTW 调整提供了尼拉帕利+AAP 与安慰剂+AAP 相比在 BRCA1/2 改变的 mCRPC 患者中的临床获益的更精确估计。结果与预设的 MVA 一致，并进一步表明调整基线不平衡的价值，特别是在较小的研究中。
NCT03748641（MAGNITUDE）。
