Durvalumab with carboplatin/paclitaxel and bevacizumab followed by durvalumab and bevacizumab with or without olaparib maintenance in newly diagnosed non-BRCA-mutated advanced ovarian cancer.

patients_and_methods

DUO-O (NCT03737643), a phase III placebo-controlledtrial, enrolled patients with newly diagnosed aOC.

DUO-O（NCT03737643）是一项III期安慰剂对照试验，招募了新诊断的aOC患者。

Following one cycle of carboplatin/paclitaxel ± bevacizumab, patients without a tumor BRCA mutation (non-tBRCAm) were randomly assigned (1 : 1 : 1) at cycle 2 to carboplatin/paclitaxel plus bevacizumab followed by bevacizumab (control); carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab plus durvalumab (durvalumab arm); or carboplatin/paclitaxel, bevacizumab plus durvalumab followed by bevacizumab, durvalumab plus olaparib (durvalumab + olaparib arm).

在完成一个周期的卡铂/紫杉醇±贝伐单抗治疗后，未发现肿瘤BRCA突变（非tBRCAm）的患者在第二个周期被随机分配（1:1:1）至卡铂/紫杉醇加贝伐单抗随后继续使用贝伐单抗（对照组）；卡铂/紫杉醇、贝伐单抗加durvalumab随后继续使用贝伐单抗加durvalumab（durvalumab组）；或卡铂/紫杉醇、贝伐单抗加durvalumab随后继续使用贝伐单抗、durvalumab加奥拉帕利（durvalumab+奥拉帕利组）。

Investigator-assessed progression-free survival(PFS; primary endpoint) was tested for the durvalumab + olaparib arm versus control in the non-tBRCAm homologous recombination deficiency (HRD)-positive and non-tBRCAm intention-to-treat(ITT) populations.

研究者评估的无进展生存期（PFS；主要终点）在非tBRCAm同源重组缺陷（HRD）阳性人群和非tBRCAm意向治疗（ITT）人群中，对durvalumab+奥拉帕利组与对照组进行了测试。

Results

One thousand one hundred and thirty patients were randomly allocated to the study.

1130名患者被随机分配到该研究中。

The prespecified interim PFS analysis [data cut-off (DCO): 5 December 2022] qualified as the primary analysis; PFS hazard ratio(HR) for the durvalumab + olaparib arm versus control was 0.49 [95% confidence interval(CI) 0.34-0.69, P < 0.0001; median (m) PFS 37.3 versus 23.0 months] in the non-tBRCAm HRD-positive and 0.63 (95% CI 0.52-0.76, P < 0.0001; mPFS 24.2 versus 19.3 months) in the non-tBRCAm ITT population.

预先设定的中期无进展生存期（PFS）分析[数据截止日期（DCO）：2022年12月5日]作为主要分析；在非tBRCA突变的HRD阳性患者中，durvalumab + olaparib组与对照组的PFS风险比（HR）为0.49 [95%置信区间（CI）0.34-0.69，P < 0.0001；中位PFS为37.3个月对比23.0个月]，在非tBRCA突变的意向治疗人群中，HR为0.63（95% CI 0.52-0.76，P < 0.0001；中位PFS为24.2个月对比19.3个月）。

For the durvalumab arm versus control, PFS HR was 0.87 (95% CI 0.73-1.04, P = 0.13; mPFS 20.6 versus 19.3 months) in the non-tBRCAm ITT population.

在非tBRCAm意向治疗人群中，与对照组相比，durvalumab组的无进展生存期（PFS）风险比（HR）为0.87（95%置信区间0.73-1.04，P=0.13；中位无进展生存期（mPFS）为20.6个月对比19.3个月）。

At final PFS and interim overall survival(OS) analysis (DCO: 18 September 2023), PFS results were consistent with primary analysis; interim OS HR for the durvalumab + olaparib arm versus control was 0.95 (95% CI 0.76-1.20, P = 0.68; 39.0% maturity) in the non-tBRCAm ITT population.

在最终的无进展生存期（PFS）和中期总生存（OS）分析中（数据截止日期：2023年9月18日），PFS结果与初步分析一致；在非tBRCAm意向治疗人群中，durvalumab加olaparib组与对照组相比，中期总生存（OS）风险比（HR）为0.95（95%置信区间0.76-1.20，P=0.68；成熟度为39.0%）。

Safety was generally consistent with the profiles of the individual agents.

安全性总体上与各单独药物的特性一致。

Conclusions

DUO-O met its primary PFS endpoints for first-line durvalumab plus carboplatin/paclitaxel and bevacizumab followed by durvalumab, bevacizumab plus olaparib maintenance versus carboplatin/paclitaxel and bevacizumab followed by bevacizumab in the non-tBRCAm HRD-positive and non-tBRCAm ITT populations.

DUO-O研究达到了其主要无进展生存期（PFS）终点，对于一线使用durvalumab联合卡铂/紫杉醇和贝伐单抗，随后使用durvalumab、贝伐单抗加奥拉帕利维持治疗，与仅使用卡铂/紫杉醇和贝伐单抗，随后仅使用贝伐单抗维持治疗相比，在非tBRCAm HRD阳性人群和非tBRCAm ITT人群中均显示出优势。

Further insight into long-term benefit is anticipated with additional follow-up.

期待随着进一步随访，对长期益处有更深入的了解。