State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, P. R. China.
Adv Ther. 2019 Dec;36(12):3368-3380. doi: 10.1007/s12325-019-01106-1. Epub 2019 Oct 10.
Seventy-five percent of ovarian cancer would relapse within 18-28 months after platinum-base chemotherapy. Evidence suggests that maintenance chemotherapy is effective in prolonging remission. Recent target therapies such as poly(ADP-ribose) polymerase inhibitors (PARPis) and angiogenesis inhibitors (AIs) are known to ease burden and recurrence of ovarian cancer. There is limited data for head-to-head comparison of PARPis, AIs, and chemotherapeutic agents (CTAs) as maintenance treatment. This network meta-analysis thus assessed the effectiveness and toxicity of these three maintenance therapies in patients with ovarian cancer.
We searched relevant sources (PubMed, EMBASE) to identify randomized controlled trials assessing efficacy and safety of maintenance therapy in patients with ovarian cancer. Primary outcome was progression-free survival (PFS) as assessed by blinded review; safety and tolerability were secondary outcomes. A network meta-analysis to compare three drug classes was performed using statistical software R.
We included 24 trials (11,366 patients) assessing efficacy and safety of PARPis (n = 4), AIs (n = 12), and CTAs (n = 8). PARPis [hazard ratio (HR) 0.64; 95% credible intervals (CrI) 0.55-0.73] and AIs (HR 0.87; 95% CrI 0.81-0.93) showed significant improvement in PFS compared to placebo but not CTA (HR 1.00; 95% CrI 0.86-1.15). PARPis showed significant improvement in PFS compared to AIs (HR 0.73; 95% CrI 0.63-0.86) and CTA (HR 0.64; 95% CrI 0.52-0.78). Adverse events (AEs) leading to treatment discontinuation and dose reduction were lower in PARPis [incidence rate ratio (IRR) 0.60; CrI 0.31-1.18 and IRR 0.73, 95% CrI 0.50-1.06, respectively] compared to AIs, but the differences were not significant.
PARPi as maintenance treatment improved PFS in ovarian cancer and was relatively safer in terms of implications caused by AEs when compared to AIs. This network meta-analysis provides valuable evidence and significant insights into treatment of ovarian cancer.
在铂类化疗后 18-28 个月内，75%的卵巢癌会复发。有证据表明，维持化疗可有效延长缓解期。最近的靶向治疗方法，如聚（ADP-核糖）聚合酶抑制剂（PARPi）和血管生成抑制剂（AIs），已被证明可以减轻卵巢癌的负担和复发。目前，PARPi、AIs 和化疗药物（CTA）作为维持治疗的头对头比较的数据有限。因此，本网络荟萃分析评估了这三种维持治疗方法在卵巢癌患者中的疗效和毒性。
我们检索了相关来源（PubMed、EMBASE），以确定评估卵巢癌患者维持治疗疗效和安全性的随机对照试验。主要结局是由盲法评估的无进展生存期（PFS）；安全性和耐受性为次要结局。使用统计软件 R 进行了比较三种药物类别的网络荟萃分析。
我们纳入了 24 项试验（11366 名患者），评估了 PARPi（n=4）、AIs（n=12）和 CTA（n=8）的疗效和安全性。PARPi [风险比（HR）0.64；95%可信区间（CrI）0.55-0.73]和 AIs（HR 0.87；95% CrI 0.81-0.93）与安慰剂相比，PFS 显著改善，但 CTA 则不然（HR 1.00；95% CrI 0.86-1.15）。PARPi 与 AIs（HR 0.73；95% CrI 0.63-0.86）和 CTA（HR 0.64；95% CrI 0.52-0.78）相比，PFS 显著改善。PARPi [发生率比（IRR）0.60；CrI 0.31-1.18 和 IRR 0.73，95% CrI 0.50-1.06]与 AIs 相比，导致治疗中断和剂量减少的不良事件（AE）发生率较低，但差异无统计学意义。
PARPi 作为维持治疗可改善卵巢癌患者的 PFS，与 AIs 相比，在 AE 引起的安全性方面具有相对优势。本网络荟萃分析为卵巢癌的治疗提供了有价值的证据和重要的见解。
