Department of Gynecology and Obstetrics, Emory University School of Medicine, Woodruff Memorial Research Bldg, 1639 Pierce Dr 4305, Atlanta, GA 30322, USA.
J Clin Oncol. 2010 Mar 1;28(7):1215-23. doi: 10.1200/JCO.2009.22.3354. Epub 2009 Nov 9.
Pertuzumab is a humanized monoclonal antibody that inhibits human epidermal growth factor receptor 2 (HER2) heterodimerization and has single-agent activity in recurrent epithelial ovarian cancer. The primary objective of this phase II study was to characterize the safety and estimate progression-free survival (PFS) of pertuzumab with gemcitabine in patients with platinum-resistant ovarian cancer.
Patients with advanced, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received a maximum of one prior treatment for recurrent cancer were randomly assigned to gemcitabine plus either pertuzumab or placebo. Collection of archival tissue was mandatory to permit exploration of biomarkers that would predict benefit from pertuzumab in this setting.
One hundred thirty patients (65 per arm) were treated. Baseline characteristics were similar between arms. The adjusted hazard ratio (HR) for PFS was 0.66 (95% CI, 0.43 to 1.03; P = .07) in favor of gemcitabine + pertuzumab. The objective response rate was 13.8% in patients who received gemcitabine + pertuzumab compared with 4.6% in patients who received gemcitabine + placebo. In patients whose tumors had low HER3 mRNA expression (< median, n = 61), an increased treatment benefit was observed in the gemcitabine + pertuzumab arm compared with the gemcitabine alone arm (PFS HR = 0.32; 95% CI, 0.17 to 0.59; P = .0002). Grade 3 to 4 neutropenia, diarrhea, and back pain were increased in patients treated with gemcitabine + pertuzumab. Symptomatic congestive heart failure was reported in one patient in the gemcitabine + pertuzumab arm.
Pertuzumab may add activity to gemcitabine for the treatment of platinum-resistant ovarian cancer. Low HER3 mRNA expression may predict pertuzumab clinical benefit and be a valuable prognostic marker.
曲妥珠单抗是一种人源化单克隆抗体，可抑制人表皮生长因子受体 2（HER2）异二聚体，并在复发性上皮性卵巢癌中具有单药活性。本Ⅱ期研究的主要目的是评估曲妥珠单抗联合吉西他滨治疗铂耐药卵巢癌患者的安全性和无进展生存期（PFS）。
入组患者为晚期铂耐药上皮性卵巢癌、输卵管癌或原发性腹膜癌，且在复发时已接受最多一次治疗。患者被随机分为吉西他滨联合曲妥珠单抗或安慰剂组。必须采集存档组织，以探索预测曲妥珠单抗在这种情况下疗效的生物标志物。
共入组 130 例患者（每组 65 例）。两组患者的基线特征相似。与吉西他滨单药组相比，吉西他滨联合曲妥珠单抗组 PFS 的调整风险比（HR）为 0.66（95%CI，0.43 至 1.03；P=0.07）。接受吉西他滨联合曲妥珠单抗治疗的患者客观缓解率为 13.8%，而接受吉西他滨联合安慰剂治疗的患者客观缓解率为 4.6%。在肿瘤 HER3mRNA 表达水平较低的患者（<中位数，n=61）中，与吉西他滨单药组相比，吉西他滨联合曲妥珠单抗组观察到治疗获益增加（PFS HR=0.32；95%CI，0.17 至 0.59；P=0.0002）。接受吉西他滨联合曲妥珠单抗治疗的患者中，3 级至 4 级中性粒细胞减少症、腹泻和背痛发生率增加，曲妥珠单抗联合吉西他滨组有 1 例患者出现症状性充血性心力衰竭。
曲妥珠单抗可能为治疗铂耐药卵巢癌增加吉西他滨的疗效。低水平的 HER3mRNA 表达可能预测曲妥珠单抗的临床获益，是一种有价值的预后标志物。
