Rucaparib maintenance for newly diagnosed advanced ovarian cancer: interim overall survival, progression-free survival, and safety at 5 years of follow-up from the phase III ATHENA-MONO/GOG-3020/ENGOT-ov45 study.

patients_and_methods

Patients were randomized 4 : 1 to oral rucaparib + intravenous (i.v.) placebo or oral + i.v. placebo.

患者按4:1的比例随机分配，口服rucaparib加静脉注射安慰剂或口服加静脉注射安慰剂。

Stratification factors were homologous recombination deficiency (HRD; BRCA mutation and loss of heterozygosity status) classification, residual disease post-chemotherapy, and surgical timing.

分层因素包括同源重组缺陷（HRD；BRCA突变和杂合性缺失状态）分类、化疗后残余疾病和手术时机。

The primary endpoint was investigator-assessed progression-free survival(invPFS) in HRD and intent-to-treat (ITT) populations.

主要终点是研究者评估的无进展生存期（invPFS），在HRD和意向治疗（ITT）人群中进行评估。

Overall survival(OS) and safety were secondary endpoints.

总生存（OS）和安全性是次要终点。

Second event of progression (PFS2) and time to first subsequent treatment (TFST) were exploratory.

进展的第二次事件（PFS2）和首次后续治疗时间（TFST）是探索性的。

Interim OS and final safety analyses data cut-off was 9 March 2023.

中期总生存和最终安全性分析的数据截止日期为2023年3月9日。

Updated invPFS, PFS2, and TFST analyses data cut-off was 5 May 2025.

更新的invPFS、PFS2和TFST分析的数据截止日期为2025年5月5日。

Results

Median invPFS follow-up was ∼59 months for both rucaparib (HRD, n = 185; ITT, n = 427) and placebo (HRD, n = 49; ITT, n = 111). invPFS was significantly longer with rucaparib versus placebo in the HRD [31.4 versus 12.0 months; hazard ratio(HR) 0.52, 95% confidence interval(CI) 0.35-0.76] and ITT (20.2 versus 9.2 months; HR 0.53, 95% CI 0.42-0.69) populations.

中位无进展生存期（invPFS）随访时间对于rucaparib（HRD，n = 185；ITT，n = 427）和安慰剂（HRD，n = 49；ITT，n = 111）均为约59个月。在HRD人群中，rucaparib组的invPFS显著长于安慰剂组[31.4个月对比12.0个月；风险比（HR）0.52，95%置信区间（CI）0.35-0.76]，在ITT人群中也是如此（20.2个月对比9.2个月；HR 0.53，95% CI 0.42-0.69）。

Interim OS was immature (OS maturity: ITT 35%) with the median (95% CI) OS not reached with rucaparib and 46.2 (34.6-not reached) months with placebo for the ITT population (HR 0.83, 95% CI 0.58-1.17).

中期总生存（OS）数据尚不成熟（OS成熟度：ITT 35%），rucaparib组的中位（95% CI）OS未达到，而安慰剂组为46.2（34.6-未达到）个月，ITT人群中rucaparib与安慰剂的总生存风险比为0.83，95%置信区间为0.58-1.17。

ITT TFST (median 23.6 versus 12.1 months) and PFS2 (35.1 versus 26.9 months) were longer with rucaparib versus placebo.

接受鲁卡帕尼治疗的患者的ITT TFST（中位数23.6个月对比12.1个月）和PFS2（35.1个月对比26.9个月）均长于接受安慰剂治疗的患者。

Overall, 34.6% of patients receiving rucaparib completed the 24-month treatment cap versus 17.3% receiving placebo.

总体而言，接受鲁卡帕尼治疗的患者中有34.6%完成了24个月的治疗期，而接受安慰剂治疗的患者中这一比例为17.3%。

As of 5 May 2025, 40.0% of patients on rucaparib were still on study and in long-term follow-up.

截至2025年5月5日，仍有40.0%的患者在接受鲁卡帕尼治疗，并处于长期随访中。

Safety remained consistent with the primary analysis.

安全性与初步分析保持一致。

Conclusions

Rucaparib monotherapy provides significant and durable long-term benefit as first-line maintenance for patients with advanced ovarian cancer with and without HRD.

作为一线维持治疗，Rucaparib单药治疗为有和没有同源重组缺陷(HRD)的晚期卵巢癌患者提供了显著且持久的长期益处。