Castro Elena, Wang Di, Walsh Sarah, Craigie Samantha, Haltner Anja, Nazari Jonathan, Niyazov Alexander, Samjoo Imtiaz A
Hospital Universitario 12 de Octubre, Madrid, Spain.
EVERSANA™, Burlington, ON, Canada.
Prostate Cancer Prostatic Dis. 2024 Dec 7. doi: 10.1038/s41391-024-00924-x.
Without head-to-head trials between talazoparib+enzalutamide (TALA + ENZA), olaparib+abiraterone acetate (OLAP + AAP), and niraparib plus AAP (NIRA + AAP) the ability to evaluate their relative efficacy as first-line (1 L) treatment in metastatic castration-resistant prostate cancer (mCRPC) is limited. The objective of this study was to assess the relative efficacy between TALA + ENZA (TALAPRO-2) versus OLAP + AAP (PROpel) and NIRA + AAP (MAGNITUDE) in 1 L mCRPC via a matching-adjusted indirect treatment comparison (MAIC).
Patient-level data from TALAPRO-2 and published data from PROpel and MAGNITUDE were used. TALAPRO-2 data were reweighted to satisfy the eligibility criteria for PROpel and MAGNITUDE. Talazoparib (0.5 mg/day) plus enzalutamide (160 mg/day) was compared to olaparib (300 mg twice daily) plus abiraterone acetate (1000 mg/day) and niraparib (200 mg/day) plus abiraterone acetate (1000 mg/day). Hazard ratios (HRs) were calculated for radiographic progression-free survival (rPFS) and overall survival (OS), and odds ratios (ORs) for prostate-specific antigen (PSA) response and objective response rate (ORR). Additional efficacy outcomes were assessed.
In all-comers, TALA + ENZA was statistically superior to OLAP + AAP for rPFS (HR: 0.727; 95% confidence interval [CI]: 0.565, 0.935) and PSA response (OR: 1.663; 1.101, 2.510), and numerically favored for OS (HR: 0.847; 0.667, 1.076) and ORR (OR: 1.109; 0.646, 1.903). In patients with homologous recombination repair mutations (HRRm), relative to NIRA + AAP, TALA + ENZA was statistically superior for rPFS (HR: 0.460; 0.280, 0.754), and numerically favored for OS (HR: 0.601; 0.347, 1.041) and ORR (OR: 1.524; 0.579, 4.016).
Results suggest that TALA + ENZA may provide improvements in clinical outcomes relative to OLAP + AAP and NIRA + AAP in 1 L mCRPC; however, inherent limitations associated with the complexity of the analyses must be considered.
由于缺乏他拉唑帕利+恩杂鲁胺（TALA + ENZA）、奥拉帕利+醋酸阿比特龙（OLAP + AAP）和尼拉帕利+醋酸阿比特龙（NIRA + AAP）之间的头对头试验，评估它们作为转移性去势抵抗性前列腺癌（mCRPC）一线（1L）治疗的相对疗效的能力有限。本研究的目的是通过匹配调整间接治疗比较（MAIC）评估TALA + ENZA（TALAPRO-2）与OLAP + AAP（PROpel）和NIRA + AAP（MAGNITUDE）在1L mCRPC中的相对疗效。
使用来自TALAPRO-2的患者水平数据以及来自PROpel和MAGNITUDE的已发表数据。对TALAPRO-2数据进行重新加权，以满足PROpel和MAGNITUDE的纳入标准。将他拉唑帕利（0.5mg/天）+恩杂鲁胺（160mg/天）与奥拉帕利（300mg，每日两次）+醋酸阿比特龙（1000mg/天）以及尼拉帕利（200mg/天）+醋酸阿比特龙（1000mg/天）进行比较。计算影像学无进展生存期（rPFS）和总生存期（OS）的风险比（HR），以及前列腺特异性抗原（PSA）反应和客观缓解率（ORR）的比值比（OR）。评估其他疗效结果。
在所有受试者中，TALA + ENZA在rPFS（HR：0.727；95%置信区间[CI]：0.565，0.935）和PSA反应（OR：1.663；1.101，2.510）方面在统计学上优于OLAP + AAP，在OS（HR：0.847；0.667，1.076）和ORR（OR：1.109；0.646，1.903）方面数值上更有利。在同源重组修复突变（HRRm）患者中，相对于NIRA + AAP，TALA + ENZA在rPFS方面在统计学上更优（HR：0.460；0.280，0.754），在OS（HR：0.601；0.347，1.041）和ORR（OR：1.
