Farletuzumab（一种拮抗叶酸受体α单克隆抗体）用于复发性的卵巢癌
Farletuzumab (a monoclonal antibody against folate receptor alpha) in relapsed platinum-sensitive ovarian cancer
Deborah K. Armstrong, Allen J. White, Susan C. Weil, Martin Phillips, Robert L. Colemand
Objective
Farletuzumab is a humanized monoclonal antibody to folate receptor-α, 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 (AUC5–6) and taxane (paclitaxel 175 mg/m2 or docetaxel 75 mg/m2), 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 (75%), comparable to that in 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.
Gynecologic Oncology
Farletuzumab治疗卵巢癌III期临床研究
III期farletuzumab研究将设置：随机、双盲、安慰剂控制等的对照。
目的：Farletuzumab是一种人源化单克隆抗体，特异靶向于叶酸受体α，在大多数上皮性卵巢癌中高度表达，而在正常组织中基本不表达。研究人员对farletuzumab单独和联合化疗用于对铂敏感的复发性卵巢癌、输卵管癌以及原发性腹膜癌患者的临床疗效进行了评估。
方法：54名合格受试者每周接受非盲的farletuzumab单独化疗或联合卡铂（AUC5-6）和紫杉烷类（紫杉醇175 mg/m2或多西紫杉醇75 mg/m2）。共进行6个周期，每个周期21天。再接受farletuzumab维持治疗直至疾病进展。28名无症状但CA125升高的复发患者先用farletuzumab单剂治疗，疾病进展后加用铂/紫杉类化疗。26名有症状的复发患者直接使用联合治疗，21名患者先用farletuzumab单剂后联合治疗。主要评估指标包括CA125、总体反应率（ORR）以及受试者第二次无进展间隔（PFI2）与其第一无进展间隔（PFI1）比较。
结果：Farletuzumab单剂使用患者耐受性良好，与化疗药联用无毒副作用。47名接受联合治疗的患者中有38名（80.9%）CA125趋于正常。在42名可评估的患者中，9名（21%）PFI2≥PFI1，优于历史比率3%。PFI1≥12个月（84%）的患者比PFI1<12个月（75%）的患者反应率高。联合治疗的完全或部分ORR为75%。
结论：研究表明，farletuzumab与卡铂和紫杉类联合用药可提高对铂敏感的复发性卵巢癌患者在缓解后6-18个月首次复发的反应率和反应时间。