Gordon Michael S, Matei Daniela, Aghajanian Carol, Matulonis Ursula A, Brewer Molly, Fleming Gini F, Hainsworth John D, Garcia Agustin A, Pegram Mark D, Schilder Russell J, Cohn David E, Roman Lynda, Derynck Mika K, Ng Kimmie, Lyons Benjamin, Allison David E, Eberhard David A, Pham Thinh Q, Dere Randall C, Karlan Beth Y
Arizona Cancer Center, Tuscon and Scottsdale, AZ, USA.
J Clin Oncol. 2006 Sep 10;24(26):4324-32. doi: 10.1200/JCO.2005.05.4221. Epub 2006 Aug 8.
Ovarian cancers (OCs) frequently have HER2 activation in the absence of HER2 overexpression. Pertuzumab, a humanized antibody that prevents HER2 dimerization and inhibits multiple HER-mediated pathways, was studied in a phase II, multicenter trial in advanced, refractory OC.
Sixty-one patients (cohort 1) with relapsed OC received a loading dose of 840 mg pertuzumab intravenously followed by 420 mg every 3 weeks; 62 patients (cohort 2) received 1,050 mg every 3 weeks. Response rate was the primary end point. Fresh tumor biopsies were obtained in cohort 1 to assay for phosphorylated HER2 (pHER2).
Median age was 57 years and median number of prior chemotherapy regimens was five. Fifty-five patients in cohort 1 and 62 patients in cohort 2 were assessable for efficacy. There were five partial responses (response rate [RR] = 4.3%; 95% CI, 1.7% to 9.4%), eight patients (6.8%) with stable disease (SD) lasting at least 6 months, and 10 patients with CA-125 reduction of at least 50% (includes two partial responses and four patients with SD > or = 6 months; total clinical activity, 14.5%). Median progression-free survival (PFS) was 6.6 weeks. Eight of 28 tumor biopsies (28.6%) were pHER2+ by enzyme-linked immunosorbent assay (ELISA; without gene amplification). Median PFS for pHER2+ patients was 20.9 weeks (n = 8) versus 5.8 weeks for pHER2- (n = 20; P = .14) and 9.1 weeks for unknown pHER2 status (n = 27). Pertuzumab was well tolerated with diarrhea in 69.1% (11.4% grade 3, no grade 4). Five patients had asymptomatic left ventricular ejection fraction decreases to less than 50% (one confirmed by central facility).
Pertuzumab is well tolerated with a RR of 4.3% in heavily-pretreated OC patients. Further studies on pHER2 as a diagnostic are warranted.
卵巢癌（OC）常常在无HER2过表达的情况下出现HER2激活。帕妥珠单抗是一种可防止HER2二聚化并抑制多种HER介导通路的人源化抗体，在一项针对晚期难治性OC的II期多中心试验中对其进行了研究。
61例复发性OC患者（队列1）静脉注射840mg帕妥珠单抗负荷剂量，随后每3周注射420mg；62例患者（队列2）每3周接受1050mg治疗。缓解率为主要终点。在队列1中获取新鲜肿瘤活检样本以检测磷酸化HER2（pHER2）。
中位年龄为57岁，既往化疗方案的中位数为5个。队列1中的55例患者和队列2中的62例患者可评估疗效。有5例部分缓解（缓解率[RR]=4.3%；95%CI，1.7%至9.4%），8例患者（6.8%）疾病稳定（SD）持续至少6个月，10例患者CA-125降低至少50%（包括2例部分缓解和4例SD≥6个月的患者；总临床活性为14.5%）。中位无进展生存期（PFS）为6.6周。通过酶联免疫吸附测定（ELISA；无基因扩增），28例肿瘤活检样本中有8例（28.6%）为pHER2阳性。pHER2阳性患者的中位PFS为20.9周（n=8），pHER2阴性患者为5.8周（n=20；P=0.14），pHER2状态未知的患者为9.1周（n=27）。帕妥珠单抗耐受性良好，69.1%的患者出现腹泻（3级为11.4%，无4级）。5例患者无症状左心室射血分数降至低于50%（1例经中心机构确认）。
帕妥珠单抗耐受性良好，在经过大量预处理的OC患者中RR为4.3%。有必要进一步研究将pHER2作为一种诊断方法。
