PURPOSE 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. EXPERIMENTAL DESIGN 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. RESULTS Baseline samples were available from 751 patients. According to our prespecified analysis plan, IL6 was predictive of a therapeutic advantage with bevacizumab for PFS (P = 0.007) and OS (P = 0.003). IL6 and OPN were found to be negative prognostic markers for both PFS and OS (P < 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. CONCLUSIONS 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.

中文翻译：

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使用卡铂和紫杉醇联合或不联合贝伐珠单抗治疗的上皮性卵巢癌患者的预测性血液生物标志物：GOG-0218 的结果。


目的 GOG-0218 是一项双盲安慰剂对照 III 期试验，比较了卡铂和紫杉醇与安慰剂、贝伐单抗随后安慰剂或贝伐单抗随后贝伐单抗治疗晚期上皮性卵巢癌 (EOC) 的效果。结果表明，贝伐珠单抗显着改善了无进展生存期 (PFS)，但总生存期 (OS) 没有改善。收集血样用于生物标志物分析。实验设计通过多重 ELISA 技术分析血浆样品中的七种预先指定的生物标志物 [IL6、Ang-2、骨桥蛋白 (OPN)、基质细胞衍生因子 1 (SDF-1)、VEGF-D、IL6 受体 (IL6R) 和GP130]。在 Cox 比例风险模型框架内，使用蛋白质标记物通过治疗相互作用项评估每种生物标记物相对于 PFS 和 OS 的预测价值。使用针对基线协变量调整的 Cox 模型来识别预后标志物。结果 基线样本来自 751 名患者。根据我们预先指定的分析计划，IL6 可以预测贝伐单抗在 PFS (P = 0.007) 和 OS (P = 0.003) 方面的治疗优势。 IL6 和 OPN 被发现是 PFS 和 OS 的阴性预后标志物 (P < 0.001)。与安慰剂相比，接受贝伐珠单抗治疗的中位 IL6 水平较高（按中位二分法）的患者具有更长的 PFS（14.2 个月与 8.7 个月）和 OS（39.6 个月与 33.1 个月）。结论 炎症细胞因子 IL6 可以预测贝伐珠单抗与卡铂和紫杉醇联合使用时的治疗效果。与接受抗血管生成疗法治疗的肾癌患者中观察到的结果一致，血浆 IL6 似乎也可以定义那些患有 EOC 的患者或多或少有可能从标准化疗中添加贝伐单抗中受益。