Division of Gynecology Oncology, Department of Obstetrics and Gynecology, Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina.
Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.
Clin Cancer Res. 2020 Mar 15;26(6):1288-1296. doi: 10.1158/1078-0432.CCR-19-0226. Epub 2020 Jan 9.
GOG-0218, a double-blind placebo-controlled phase III trial, compared carboplatin and paclitaxel with placebo, bevacizumab followed by placebo, or bevacizumab followed by bevacizumab in advanced epithelial ovarian cancer (EOC). Results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with bevacizumab. Blood samples were collected for biomarker analyses.
Plasma samples were analyzed via multiplex ELISA technology for seven prespecified biomarkers [IL6, Ang-2, osteopontin (OPN), stromal cell-derived factor-1 (SDF-1), VEGF-D, IL6 receptor (IL6R), and GP130]. The predictive value of each biomarker with respect to PFS and OS was assessed using a protein marker by treatment interaction term within the framework of a Cox proportional hazards model. Prognostic markers were identified using Cox models adjusted for baseline covariates.
Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS ( = 0.007) and OS ( = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS ( < 0.001). Patients with high median IL6 levels (dichotomized at the median) treated with bevacizumab had longer PFS (14.2 vs. 8.7 months) and OS (39.6 vs. 33.1 months) compared with placebo.
The inflammatory cytokine IL6 may be predictive of therapeutic benefit from bevacizumab when combined with carboplatin and paclitaxel. Aligning with results observed in patients with renal cancer treated with antiangiogenic therapies, it appears plasma IL6 may also define those patients with EOC more or less likely to benefit from the addition of bevacizumab to standard chemotherapy.
GOG-0218 是一项双盲安慰剂对照的 III 期临床试验，比较了卡铂和紫杉醇联合安慰剂、贝伐珠单抗联合安慰剂或贝伐珠单抗联合贝伐珠单抗治疗晚期上皮性卵巢癌（EOC）。结果表明，贝伐珠单抗显著改善了无进展生存期（PFS），但对总生存期（OS）没有获益。采集了血液样本进行生物标志物分析。
通过多指标酶联免疫吸附试验技术分析血浆样本，检测了 7 个预先指定的生物标志物[白细胞介素 6（IL6）、血管生成素 2（Ang-2）、骨桥蛋白（OPN）、基质细胞衍生因子-1（SDF-1）、血管内皮生长因子-D（VEGF-D）、白细胞介素 6 受体（IL6R）和 gp130]。在 Cox 比例风险模型框架内，使用治疗与生物标志物相互作用项评估每个生物标志物对 PFS 和 OS 的预测价值。使用 Cox 模型识别预后标志物，模型调整了基线协变量。
共有 751 名患者的基线样本可用。根据我们预先指定的分析计划，IL6 是贝伐珠单抗治疗 PFS（=0.007）和 OS（=0.003）获益的预测因子。IL6 和 OPN 是 PFS 和 OS 的负预后标志物（<0.001）。中位 IL6 水平较高（中位数二分位数）的患者接受贝伐珠单抗治疗，PFS（14.2 个月比 8.7 个月）和 OS（39.6 个月比 33.1 个月）均长于安慰剂组。
炎症细胞因子 IL6 可能是贝伐珠单抗联合卡铂和紫杉醇治疗获益的预测因子。与接受抗血管生成治疗的肾癌患者观察到的结果一致，似乎 EOC 患者的血浆 IL6 水平也可能确定其是否更有可能从贝伐珠单抗联合标准化疗中获益。
