Berek Jonathan, Taylor Peyton, McGuire William, Smith L Mary, Schultes Birgit, Nicodemus Christopher F
Division of Gynecologic Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.
J Clin Oncol. 2009 Jan 20;27(3):418-25. doi: 10.1200/JCO.2008.17.8400. Epub 2008 Dec 15.
This phase III study tested the hypothesis that the CA-125-specific murine monoclonal antibody, oregovomab, administered as a monoimmunotherapy after front-line therapy in a selected ovarian cancer population would prolong time to relapse (TTR) and, ultimately, survival.
Patients with stage III to IV ovarian cancer with preoperatively elevated CA-125 and objectively defined characteristics were randomly assigned 4 to 12 weeks after front-line carboplatin and paclitaxel chemotherapy to maintenance monoimmunotherapy in a fully blinded protocol. Two mg of oregovomab or placebo was infused over 20 minutes at weeks 0, 4, and 8 and then 12 weeks until recurrence or up to year 5. Patients were evaluated with serial imaging and clinical evaluation for evidence of recurrence at quarterly visits. TTR was the primary end point.
Three hundred seventy-three patients were accrued at more than 60 centers; 251 patients were assigned to oregovomab and 120 patients were assigned to placebo. The treatment arms were well balanced. There were no differences in the clinical outcomes between treatment groups. Median TTR measured from randomization after completion of chemotherapy for the integrated study was 10.3 months (95% CI, 9.7 to 13.0 months) for oregovomab and 12.9 months (95% CI, 10.1 to 17.4 months) for placebo (P = .29, log-rank test). The treatment was well tolerated. Grade 3 to 4 toxicity was reported in 24.6% of patients in the placebo group and 20.1% of patients in the oregovomab group, respectively.
Although oregovomab has demonstrated bioactivity, the strategy of monoimmunotherapy is not effective as maintenance therapy after front-line treatment of a favorable subset of patients with advanced ovarian cancer. Future studies of this or other tumor-antigen specific immunization strategies should seek ways to further augment induced immunity.
本III期研究检验了以下假设，即在选定的卵巢癌患者群体中，一线治疗后给予CA-125特异性鼠单克隆抗体奥瑞珠单抗进行单免疫治疗，可延长复发时间（TTR）并最终延长生存期。
术前CA-125升高且具有客观定义特征的III至IV期卵巢癌患者，在一线卡铂和紫杉醇化疗后4至12周，按照完全盲法方案随机分配接受维持单免疫治疗。在第0、4和8周，然后在第12周直至复发或长达5年，在20分钟内输注2毫克奥瑞珠单抗或安慰剂。每季度随访时，通过系列影像学检查和临床评估对患者进行复发证据评估。TTR是主要终点。
60多个中心共纳入373例患者；251例患者被分配接受奥瑞珠单抗治疗，120例患者被分配接受安慰剂治疗。治疗组间均衡性良好。治疗组之间的临床结局无差异。综合研究中，从化疗完成后随机分组开始测量的奥瑞珠单抗组中位TTR为10.3个月（95%CI，9.7至13.0个月），安慰剂组为12.9个月（95%CI，10.1至17.4个月）（P = 0.29，对数秩检验）。该治疗耐受性良好。安慰剂组和奥瑞珠单抗组分别有24.6%和20.1%的患者报告有3至4级毒性。
尽管奥瑞珠单抗已显示出生物活性，但单免疫治疗策略作为晚期卵巢癌有利亚组患者一线治疗后的维持治疗并不有效。未来对这种或其他肿瘤抗原特异性免疫策略的研究应寻求进一步增强诱导免疫的方法。
