Oncology Unit, ARNAS Civico, Palermo, Italy.
IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori, Meldola, Italy.
Eur Urol Oncol. 2024 Apr;7(2):179-188. doi: 10.1016/j.euo.2023.07.013. Epub 2023 Aug 12.
PARP inhibitors (PARPi) are established treatments for metastatic castration-resistant prostate cancer (mCRPC) with homologous recombination repair (HRR) deficiency after androgen receptor signalling inhibitor (ARSI) failure. New PARPi + ARSI combinations have been tested in all comers, although their clinical relevance in HRR-proficient tumours remains uncertain.
To quantitatively synthesise evidence from randomised trials assessing the efficacy and safety of PARPi + ARSI combinations for first-line treatment of mCRPC.
We searched the PubMed, EMBASE, SCOPUS, and Cochrane Library databases up to February 28, 2023. Randomised controlled trials (RCTs) comparing PARPi + ARSI versus placebo + ARSI for first-line treatment of mCRPC were eligible. Two reviewers independently performed screening and data extraction and assessed the risk of bias, while a third reviewer evaluated the eligibility criteria.
Overall, three phase 3 RCTs were included in the systematic review: PROPEL, MAGNITUDE, and TALAPRO-2. A total of 2601 patients with mCRPC were enrolled. Two of these trials (PROPEL and TALAPRO-2) assessed the radiographic progression-free survival benefit of PARPi + ARSI for first-line treatment of mCRPC, independent of HRR status. The pooled hazard ratio was 0.62 (95% confidence interval 0.53-0.72). The pooled hazard ratio for overall survival was 0.84 (95% confidence interval 0.72-0.98), indicating a 16% reduction in the risk of death among patients who received the combination.
Results from this meta-analysis support the use of ARSI + PARPi combinations in biomarker-unselected mCRPC. However, such combinations might be less clinically relevant in HRR-proficient cancers, especially considering the change in treatment landscape for mCRPC.
We looked at outcomes from trials testing combinations of two classes of drugs (PARP inhibitors and ARSI) in advanced prostate cancer. We found that these combinations seem to work regardless of gene mutations identified as biomarkers of response to PARP inhibitors when used on their own.
聚腺苷二磷酸核糖聚合酶抑制剂（PARPi）是雄激素受体信号抑制剂（ARSI）失败后同源重组修复（HRR）缺陷的转移性去势抵抗性前列腺癌（mCRPC）的既定治疗方法。已经在所有患者中测试了新的 PARPi+ARSI 联合治疗，但它们在 HRR 阳性肿瘤中的临床相关性仍不确定。
定量综合评估 PARPi+ARSI 联合治疗 mCRPC 一线治疗的疗效和安全性的随机试验证据。
我们检索了 PubMed、EMBASE、SCOPUS 和 Cochrane 图书馆数据库，检索时间截至 2023 年 2 月 28 日。纳入比较 PARPi+ARSI 与安慰剂+ARSI 一线治疗 mCRPC 的随机对照试验（RCT）。两名评审员独立进行筛选和数据提取，并评估偏倚风险，而第三名评审员评估纳入标准。
系统评价共纳入三项 III 期 RCT：PROPEL、MAGNITUDE 和 TALAPRO-2。共纳入 2601 例 mCRPC 患者。其中两项试验（PROPEL 和 TALAPRO-2）评估了 PARPi+ARSI 一线治疗 mCRPC 的放射学无进展生存期获益，与 HRR 状态无关。汇总的风险比为 0.62（95%置信区间 0.53-0.72）。总生存期的汇总风险比为 0.84（95%置信区间 0.72-0.98），表明接受联合治疗的患者死亡风险降低了 16%。
这项荟萃分析的结果支持在无生物标志物选择的 mCRPC 中使用 ARSI+PARPi 联合治疗。然而，在 HRR 阳性癌症中，此类联合治疗的临床相关性可能较低，尤其是考虑到 mCRPC 治疗领域的变化。
我们研究了两种药物（PARP 抑制剂和 ARSI）联合治疗晚期前列腺癌的试验结果。我们发现，这些组合似乎有效，无论单独使用 PARP 抑制剂时作为反应生物标志物识别的基因突变如何。
