Hettle Robert, McCrea Charles, Lee Chee Khoon, Davidson Richard
Health Economics and Payer Evidence, AstraZeneca, Academy House, 136 Hills Road, Cambridge, Cambridgeshire CB2 8PA, UK.
Health Economics and Payer Evidence, AstraZeneca, Cambridge, UK.
Ther Adv Med Oncol. 2021 Sep 30;13:17588359211049639. doi: 10.1177/17588359211049639. eCollection 2021.
In patients with newly diagnosed ovarian cancer, bevacizumab and poly(ADP-ribose) polymerase (PARP) inhibitors, alone or in combination, have shown benefit as maintenance treatment following platinum-based chemotherapy. However, no trials have compared a PARP inhibitor plus bevacizumab a PARP inhibitor, or a PARP inhibitor bevacizumab. We performed an unanchored population-adjusted indirect treatment comparison to estimate the relative efficacy and safety of maintenance treatments for newly diagnosed advanced ovarian cancer.
Analyses were performed using aggregate data from the PRIMA trial and patient-level data from a subset of patients from the PAOLA-1 trial that met surgery and staging eligibility criteria of PRIMA. Propensity weights were used to match baseline characteristics of the PAOLA-1 subset to those of the PRIMA population. Analysis was performed in overall (biomarker-unselected) and homologous recombination repair deficiency (HRD)-positive populations.
A total of 595/806 (266/387 HRD-positive) PAOLA-1 patients were included. After matching, the effective sample size for PAOLA-1 was 532 (242 HRD-positive). Maintenance olaparib plus bevacizumab reduced the risk of disease progression or death by 43% [hazard ratio (HR) 0.57; 95% confidence interval (CI): 0.47-0.69] niraparib and by 40% (HR 0.60; 95% CI: 0.49-0.74) bevacizumab in the biomarker-unselected population and by 43% (HR 0.57; 95% CI: 0.41-0.79) and 60% (HR 0.40; 95% CI: 0.29-0.55), respectively, in the HRD-positive population. Progression-free survival (PFS) benefits of maintenance niraparib and bevacizumab arms were comparable in the biomarker-unselected population (HR 1.07; 95% CI: 0.87-1.32); however, niraparib showed a 30% reduced risk compared with bevacizumab (HR 0.70; 95% CI: 0.51-0.97) in the HRD-positive population.
In biomarker-unselected and HRD-positive patients, combination treatment with olaparib plus bevacizumab as maintenance treatment improves PFS for women with newly diagnosed advanced ovarian cancer compared with either bevacizumab or niraparib alone. Results are hypothesis generating and could guide randomised trial design.
在新诊断的卵巢癌患者中，贝伐单抗和聚（ADP - 核糖）聚合酶（PARP）抑制剂单独或联合使用，作为铂类化疗后的维持治疗已显示出益处。然而，尚无试验比较PARP抑制剂加贝伐单抗、PARP抑制剂或PARP抑制剂与贝伐单抗。我们进行了一项非锚定的人群调整间接治疗比较，以估计新诊断的晚期卵巢癌维持治疗的相对疗效和安全性。
使用PRIMA试验的汇总数据和PAOLA - 1试验中符合PRIMA手术和分期资格标准的部分患者的个体水平数据进行分析。倾向权重用于使PAOLA - 1子集的基线特征与PRIMA人群的基线特征相匹配。在总体（生物标志物未选择）和同源重组修复缺陷（HRD）阳性人群中进行分析。
共纳入595/806例（266/387例HRD阳性）PAOLA - 1患者。匹配后，PAOLA - 1的有效样本量为532例（242例HRD阳性）。在生物标志物未选择的人群中，维持奥拉帕利加贝伐单抗使疾病进展或死亡风险降低43%[风险比（HR）0.57；95%置信区间（CI）：0.47 - 0.69]，优于尼拉帕利，降低40%（HR 0.60；95% CI：0.49 - 0.74）优于贝伐单抗；在HRD阳性人群中，分别降低43%（HR 0.57；95% CI：0.41 - 0.79）和60%（HR 0.40；95% CI：0.29 - 0.55）。在生物标志物未选择的人群中，维持尼拉帕利和贝伐单抗组的无进展生存期（PFS）益处相当（HR 1.07；95% CI：0.87 - 1.32）；然而，在HRD阳性人群中，尼拉帕利与贝伐单抗相比风险降低30%（HR 0.70；95% CI：0.51 - 0.97）。
在生物标志物未选择和HRD阳性的患者中，与单独使用贝伐单抗或尼拉帕利相比，奥拉帕利加贝伐单抗联合治疗作为维持治疗可改善新诊断的晚期卵巢癌女性的PFS。结果为假设生成，可指导随机试验设计。
