Primary Analysis of EPIK-O/ENGOT-ov61: Alpelisib Plus Olaparib Versus Chemotherapy in Platinum-Resistant or Platinum-Refractory High-Grade Serous Ovarian Cancer Without BRCA Mutation.

We report efficacy and biomarker data from EPIK-O, which investigated alpelisib + olaparib versus single-agent chemotherapy in these patients.

我们报告了EPIK-O研究的疗效和生物标志物数据，该研究调查了阿帕他胺联合奥拉帕利与单药化疗在这些患者中的效果。

patients_and_methods

EPIK-O was an open-label, phase III trial that randomly assigned patients with platinum-resistant/platinum-refractory HGSOC with no germline or known somatic BRCA mutation 1:1 to alpelisib 200 mg once daily + olaparib 200 mg twice daily or treatment of physician's choice (TPC; paclitaxel 80 mg/m2 once weekly or pegylated liposomal doxorubicin 40-50 mg/m2 once every 28 days).

EPIK-O 是一项开放标签、III 期试验，随机分配了既往对铂类耐药/铂类难治性高级别浆液性卵巢癌（HGSOC）患者，且无胚系或已知体细胞 BRCA 突变的患者，按照 1:1 的比例接受每日一次 200 mg 阿帕替尼加每日两次 200 mg 奥拉帕利，或医生选择的治疗（TPC；每周一次 80 mg/m2 的紫杉醇或每 28 天一次 40-50 mg/m2 的聚乙二醇脂质体多柔比星）。

Patients had 1-3 previous systemic therapies.

患者之前接受过 1-3 种系统性治疗。

Previous bevacizumab was required (unless contraindicated); previous poly(adenosine diphosphate-ribose) polymerase inhibitors were allowed.

除非有禁忌症，之前必须使用贝伐单抗；允许使用之前的聚腺苷二磷酸核糖聚合酶抑制剂。

Primary end point was progression-free survival(PFS) per RECIST 1.1 (blinded independent review committee [BIRC]).

主要终点是根据RECIST 1.1标准（盲独立评审委员会[BIRC]）评估的无进展生存期（PFS）。

Secondary efficacy end points included overall response rate (ORR; per BIRC), duration of response (per BIRC), and overall survival(OS; key secondary end point).

次要疗效终点包括总体反应率（ORR; 根据独立评审委员会（BIRC）评估）、反应持续时间（根据BIRC评估）和总生存期（OS; 关键次要终点）。

Results

A total of 358 patients (alpelisib + olaparib [n = 180], TPC [n = 178]) were included.

共有358名患者（阿帕他胺 + 奥拉帕尼组[n = 180]，对照组[n = 178]）被纳入研究。

The median follow-up time was 9.3 months.

中位随访时间为9.3个月。

At data cutoff (April 21, 2023), 33 (18.3%) and 30 (16.9%) patients remained on treatment with alpelisib + olaparib and TPC, respectively.

截止至2023年4月21日数据截断时，分别有33名（18.3%）和30名（16.9%）患者仍在接受alpelisib + olaparib和TPC治疗。

The median PFS (BIRC) was 3.6 versus 3.9 months (hazard ratio[HR], 1.14 [95% CI, 0.88 to 1.48]; one-sided P = .84) for alpelisib + olaparib versus TPC.

中位无进展生存期（BIRC评估）为3.6个月对比3.9个月（风险比[HR]，1.14 [95% 置信区间，0.88至1.48]；单侧P = .84），对于alpelisib + olaparib对比TPC。

The ORR was 15.6% (95% CI, 10.6% to 21.7%) versus 13.5% (95% CI, 8.8% to 19.4%).

客观缓解率（ORR）为15.6%（95% 置信区间，10.6%至21.7%）对比13.5%（95% 置信区间，8.8%至19.4%）。

The median OS was 10.0 versus 10.6 months (HR, 1.22; 95% CI, 0.87 to 1.71).

中位总生存期为10.0个月对比10.6个月（风险比，1.22；95%置信区间，0.87至1.71）。

The safety profile of alpelisib + olaparib was consistent with that observed for the individual agents.

阿帕他胺联合奥拉帕利的安全性特征与单独使用这些药物时观察到的一致。

Conclusions

The primary objective, PFS improvement, was not met in EPIK-O.

主要研究终点，无进展生存期（PFS）的改善，在EPIK-O研究中未达成。

No new or unexpected adverse events were observed.

在EPIK-O研究中未观察到新的或意外的不良事件。

Biomarker analyses provided new insights for responders to alpelisib + olaparib.

生物标志物分析为对阿帕他胺加奥拉帕利反应者提供了新的见解。