Christinat Yann, Labidi-Galy Intidhar, Ho Liza, Clément Sophie, Genestie Catherine, Sehouli Jalid, Cinieri Saverio, Gonzalez-Martin Antonio, Kolovetsiou-Kreiner Vassiliki, Fujiwara Keiichi, Von Gorp Toon, Tognon Germana, Hietanen Sakari, Heinzelmann-Schwarz Viola, Ray-Coquard Isabelle, Pujade-Lauraine Eric, McKee Thomas A
Department of Clinical Pathology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
Department of Oncology, Hôpitaux Universitaires de Genève, Geneva, Switzerland.
JCO Precis Oncol. 2025 Jul;9:e2400825. doi: 10.1200/PO-24-00825. Epub 2025 Jul 2.
The ability of the Geneva homologous recombination deficiency (HRD) test to predict progression-free survival (PFS) in patients with high-grade ovarian cancer treated with poly (ADP-ribose) polymerase inhibitors has been demonstrated. Its performance with respect to overall survival (OS) has not been assessed yet.
Using the final results of the PAOLA-1/ENGOT-ov25 phase III clinical trial with a median follow-up of 5 years, we evaluated the Geneva HRD test on 468 samples as part of the ENGOT HRD European Initiative. Results were evaluated in terms of final PFS and OS in the olaparib + bevacizumab and placebo + bevacizumab arms and compared with the Myriad MyChoice HRD test.
Final PFS was consistent with previously published data and confirmed the predictive value of the Geneva HRD test with a hazard ratio (HR) of 0.41 (95% CI, 0.30 to 0.57) for HRD-positive patients. The results for OS showed a HR of 0.56 (95% CI, 0.37 to 0.85) for HRD-positive patients and 1.6 (95% CI, 1.1 to 2.3) for HRD-negative patients. These results are consistent with those observed with the Myriad test, including the negative OS trend in the HRD-negative subgroup treated with olaparib + bevacizumab (HR, 1.2 [95% CI, 0.83 to 1.8]). A subgroup analysis of patients with intermediate HRD scores showed that the normalized large-scale state transition score used by the Geneva HRD test had both predictive and prognostic value.
The Geneva HRD test predicts PFS and OS benefit from olaparib + bevacizumab. The potential detrimental effect of olaparib + bevacizumab on OS in the HRD-negative population is hypothesis-generating and needs to be confirmed prospectively.
已证实日内瓦同源重组缺陷（HRD）检测能够预测接受聚（ADP - 核糖）聚合酶抑制剂治疗的高级别卵巢癌患者的无进展生存期（PFS）。但其对总生存期（OS）的表现尚未得到评估。
利用PAOLA - 1/ENGOT - ov25 III期临床试验的最终结果，该试验中位随访时间为5年，作为ENGOT HRD欧洲倡议的一部分，我们对468份样本进行了日内瓦HRD检测。根据奥拉帕利+贝伐单抗组和安慰剂+贝伐单抗组的最终PFS和OS对结果进行评估，并与Myriad MyChoice HRD检测进行比较。
最终PFS与先前发表的数据一致，并证实了日内瓦HRD检测对HRD阳性患者的预测价值，风险比（HR）为0.41（95%CI，0.30至0.57）。OS结果显示，HRD阳性患者的HR为0.56（95%CI，0.37至0.85），HRD阴性患者的HR为1.6（95%CI，1.1至2.3）。这些结果与Myriad检测观察到的结果一致，包括在接受奥拉帕利+贝伐单抗治疗的HRD阴性亚组中OS呈阴性趋势（HR，1.2[95%CI，0.83至1.8]）。对HRD评分中等的患者进行亚组分析表明，日内瓦HRD检测使用的标准化大规模状态转换评分具有预测和预后价值。
日内瓦HRD检测可预测奥拉帕利+贝伐单抗带来的PFS和OS获益。奥拉帕利+贝伐单抗对HRD阴性人群OS的潜在有害影响仅为一种假设，需要前瞻性地予以证实。
