Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer
Oregovomab Maintenance Monoimmunotherapy Does Not Improve Outcomes in Advanced Ovarian Cancer
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DOI：
10.1200/jco.2008.17.8400
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发表时间：
2009-01-20
影响因子：
45.3
通讯作者：
Nicodemus, Christopher F.
中科院分区：
文献类型：
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作者：
Berek, Jonathan;Taylor, Peyton;Nicodemus, Christopher F.
这项III期研究验证了这样一种假设，即在选定的卵巢癌患者中，在一线治疗后给予CA-125特异性鼠类单抗oregoomab作为单一免疫治疗可以延长复发时间(TTR)，并最终延长患者的生存时间。患者和方法将手术前CA-125升高且具有客观特征的III至IV期卵巢癌患者随机分配到卡铂和紫杉醇一线化疗后4-12周，以完全盲法方案维持单一免疫治疗。在0周、4周、8周、12周和5岁时，静脉滴注2 mg oregoomab或安慰剂超过20分钟，直到复发或5岁。患者在每季度就诊时进行系列成像和临床评估，以寻找复发的证据。结果在60多个中心共收集了373名患者，251名患者被分配到oregoomab组，120名患者被分配到安慰剂组。治疗臂平衡得很好。治疗组之间的临床结果没有差异。在综合研究中，化疗结束后随机抽样测得的中位TTRoregoomab为10.3个月(95%可信区间，9.7~13.0个月)，安慰剂组为12.9个月(95%可信区间，10.1~17.4个月)(P=0.29，LOG-RANK检验)。治疗耐受性良好。安慰剂组和oregoomab组的3~4级毒性发生率分别为24.6%和20.1%。结论oregoomab虽然显示出生物活性，但作为一线治疗的有利亚群的晚期卵巢癌患者，单一免疫治疗策略并不是有效的维持治疗。未来对这种或其他肿瘤抗原特异性免疫策略的研究应该寻找进一步增强诱导免疫的方法。
PurposeThis 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 and MethodsPatients 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.ResultsThree 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.ConclusionAlthough 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.