Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer
Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer
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DOI：
10.1016/j.ygyno.2013.03.002
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发表时间：
2013-06-01
影响因子：
4.7
通讯作者：
Coleman, Robert L.
中科院分区：
文献类型：
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作者：
Armstrong, Deborah K.;White, Allen J.;Coleman, Robert L.
目标。Farletuzumab是一种叶酸受体α的人源化单克隆抗体，叶酸受体α在大多数上皮性卵巢癌中过表达，但在正常组织中基本不存在。我们评估了farletuzumab单独和联合化疗在首次复发、铂敏感的卵巢癌、输卵管癌和原发性腹膜癌女性患者中的临床活性。54名符合条件的受试者每周接受开放标签法来珠单抗治疗，单药或联合卡铂（AUC(5-6)）和紫杉烷(紫杉醇175 mg/m(2)或多西他赛75 mg/m(2))，每21天接受一次，共6个周期，随后进行法来珠单抗维持，直至进展。28例无症状CA125复发患者接受单药法妥珠单抗治疗，并可接受铂/紫杉烷化疗。单药进展后加上farletuzumab。26例有症状复发的患者直接进入联合组；单一药剂后进入21名受试者。主要终点包括归一化CA125和总有效率（ORR）。每个受试者的第二次无进展间期（PFI2）的持续时间与她自己的第一反应间期（PFI1）进行比较。Farletuzumab作为单药耐受性良好，与化疗一起使用时无附加毒性。47名接受法妥珠单抗联合化疗的患者中，38名（80.9%）CA125正常化。在9/42（21%）可评估受试者中，PFI2为>= PFI1，优于历史发生率（3%）。反响很好；PFI1 = 12个月的比例（84%）。联合治疗的全部或部分ORR为75%。基于该研究，farletuzumab联合卡铂和紫杉烷可提高铂敏感卵巢癌患者缓解后6-18个月首次复发的缓解率和缓解持续时间，(C) 2013 Elsevier Inc.。版权所有。
Objective. Farletuzumab is a humanized monoclonal antibody to folate receptor-alpha, which is over-expressed in most epithelial ovarian cancers but largely absent on normal tissue. We evaluated clinical activity of farletuzumab, alone and combined with chemotherapy, in women with first-relapse, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancers.Methods. Fifty-four eligible subjects received open-label farletuzumab weekly, single agent or combined with carboplatin (AUC(5-6)) and taxane (paclitaxel 175 mg/m(2) or docetaxel 75 mg/m(2)), every 21 days for 6 cycles, followed by farletuzumab maintenance until progression. Twenty-eight subjects with asymptomatic CA125 relapse received single-agent farletuzumab and could receive platinum/taxane chemotherapy. plus farletuzumab after single-agent progression. Twenty-six subjects with symptomatic relapse entered the combination arm directly; 21 subjects entered after single agent. Primary endpoints included normalized CA125 and Overall Response Rate (ORR). Duration of each subject's second progression-free interval (PFI2) was compared with her own first response interval (PFI1).Results. Farletuzumab was well-tolerated as single agent, without additive toxicity when administered with chemotherapy. Of 47 subjects who received farletuzumab with chemotherapy, 38 (80.9%) normalized CA125. In 9/42 (21%) evaluable subjects, PFI2 was >= PFI1, better than the historical rate (3%). There was a high response ;rate among subjects with PFI1 = 12 months (84%). Complete or partial ORR was 75% with combination therapy.Conclusion. Based on this study, farletuzumab with carboplatin and taxane may enhance the response rate and duration of response in platinum-sensitive ovarian cancer patients with first relapse after remission of 6-18 months, (C) 2013 Elsevier Inc. All rights reserved.