在卵巢癌患者中，根据患者特定生物标志物状况选择合适的伴随药物与聚腺苷二磷酸核苷酸聚合酶（PARP）抑制剂联合使用，可能有助于提高治疗效果。然而，在卵巢癌患者中，针对同源重组修复（HRR）基因突变，不同PARP抑制剂基于组合疗法的疗效和安全性尚未得到评估。在韩国妇科肿瘤研究组（KGOG）3045的一个子研究中，我们比较了基于奥拉帕利布的两种组合疗法的疗效和安全性，并评估了铂耐药卵巢癌患者中HRR基因突变的生物标志物。患者随机分配到奥拉帕利布（200毫克，每天两次）+西达利尼布（30毫克，每天一次）组（组1，n = 16）或奥拉帕利布（300毫克）+度瓦鲁玛布（1,500毫克，每4周一次）组（组2，n = 14）。组1和组2的客观缓解率分别为50.0％和42.9％。大多数患者（83.3％）具有BRCA突变，分布在两组间相似。37.5％的患者和35.7％的患者观察到3级或4级与治疗相关的不良事件，但所有事件均得到了妥善处理。组1中，高血管内皮生长因子标志与良好的治疗效果相关，在组2中，免疫标志物（PD-L1表达[CPS ≥ 10]，CD8，嗜中性粒细胞/淋巴细胞比和血小板/淋巴细胞比）与良好的治疗效果相关。疾病进展时同源重组信号通路的激活与对后续治疗的差效应有关。基于包括免疫组织化学、全外显子和RNA测序以及全血样本分析的全面生物标志物分析，我们确定了可以帮助判断患者生物标志物状况并选择合适的两种组合策略的标志物。我们的研究结果有望改善PARP抑制剂时代卵巢癌患者的治疗结果。© 2023 UICC.

Choosing an optimal concomitant drug for combination with poly-ADP ribose polymerase (PARP) inhibitor based on patient-specific biomarker status may help increase to improve treatment efficacy in patients with ovarian cancer. However, the efficacy and safety of different PARP inhibitor-based combinations in patients with homologous recombination repair (HRR) mutations have not been evaluated in ovarian cancer. In this sub-study of Korean Gynecologic Oncology Group (KGOG) 3045, we compared the efficacy and safety of two olaparib-based combinations and biomarkers of patients with platinum-resistant ovarian cancer with HRR gene mutations. Patients were randomized to receive either olaparib (200 mg twice a day) + cediranib (30 mg daily) (Arm 1, n = 16) or olaparib (300 mg) + durvalumab (1,500 mg once every 4 weeks) (Arm 2, n = 14). The objective response rates for Arm 1 and Arm 2 were 50.0% and 42.9%, respectively. Most patients (83.3%) had BRCA mutations, which were similarly distributed between arms. Grade 3 or 4 treatment-related adverse events were observed in 37.5% and 35.7% of the patients, respectively, but all were managed properly. A high vascular endothelial growth factor signature was associated with favorable outcomes in Arm 1, whereas immune markers (PD-L1 expression [CPS ≥10], CD8, neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio) were associated with favorable outcomes in Arm 2. The activation of homologous recombination pathway upon disease progression was associated with poor response to subsequent therapy. Based on comprehensive biomarker profiling, including immunohistochemistry, whole-exome and RNA sequencing and whole blood-based analyses, we identified biomarkers that could help inform which of the two combination strategies is appropriate given a patient's biomarker status. Our findings have the potential to improve treatment outcome for patients with ovarian cancer in the PARP inhibitor era.© 2023 UICC.