Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK
Cancer Research UK and UCL Cancer Trials Centre, University College London, London, UK.
Int J Gynecol Cancer. 2024 Aug 5;34(8):1225-1231. doi: 10.1136/ijgc-2023-005200.
Immunotherapy directed at 5T4 tumor antigen may delay the need for further chemotherapy. An attenuated modified vaccinia Ankara virus containing the gene encoding for 5T4 (MVA-5T4) was studied in asymptomatic relapsed ovarian cancer.
To assess the effectiveness and safety of MVA-5T4 as treatment for asymptomatic relapsed ovarian cancer.
TRIOC was a phase II randomized (1:1), placebo-controlled, double-blind multicenter study. The primary aim was to assess the effectiveness and safety of MVA-5T4 as a treatment for asymptomatic patients with relapsed ovarian cancer. Eligible patients had International Federation of Gynecology and Obstetrics (FIGO) stage IC1-III or IVA epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, Eastern Cooperative Oncology Group (ECOG) 0-1, with relapse defined by a rise in CA-125 to twice the upper limit of normal or low-volume disease on CT scan. The primary endpoint was disease progression (including deaths from ovarian cancer) at 25 weeks. Following a brief suspension, the trial restarted as a single-arm study. The revised single-arm design required 45 evaluable patients treated with MVA-5T4 to detect a 25-week progression rate of 50%, assuming an expected 70% rate without MVA-5T4; 85% power with one-sided 5% significance.
A total of 94 eligible patients were recruited, median age was 65 years (range 42-82), median follow-up 34 months (range 2-46). Overall, 59 patients received MVA-5T4 and 35 patients received placebo. The median number of MVA-5T4 injections received was 7 (range 0-9), compared with a median of 6 (range 1-12) for patients receiving placebo. Median progression-free survival was the same in both arms (3.0 months). The 25-week progression rate was similar in both arms: 80.0% for patients treated with MVA-5T4 and 85.7% for those receiving placebo (risk difference -5.7%, 95% CI -21.4% to 10.0%). Median time to clinical intervention was improved with MVA-5T4: 7.6 months (range 6.7-9.5) vs 5.6 (range 4.9-7.6), CONCLUSION: MVA-5T4 vaccination in patients with asymptomatic relapse was well-tolerated but did not improve the progression rate at 25 weeks. The majority of patients who received MVA-5T4 had clinical intervention later than those assigned to placebo.
NCT01556841.
针对 5T4 肿瘤抗原的免疫疗法可能会延迟进一步化疗的需要。一种含有编码 5T4 基因的减毒改良安卡拉痘苗病毒（MVA-5T4）已在无症状复发性卵巢癌中进行了研究。
评估 MVA-5T4 作为治疗无症状复发性卵巢癌的有效性和安全性。
TRIOC 是一项 II 期随机（1:1）、安慰剂对照、双盲多中心研究。主要目的是评估 MVA-5T4 作为治疗无症状复发性卵巢癌患者的有效性和安全性。符合条件的患者为国际妇产科联合会（FIGO）分期 IC1-III 或 IVA 上皮性卵巢、输卵管或原发性腹膜癌，东部合作肿瘤学组（ECOG）0-1，复发定义为 CA-125 升高至正常值上限的两倍或 CT 扫描显示低容量疾病。主要终点是 25 周时的疾病进展（包括卵巢癌死亡）。在短暂暂停后，该试验重新作为单臂研究进行。修订后的单臂设计需要 45 名接受 MVA-5T4 治疗的可评估患者，以检测 25 周时的进展率为 50%，假设不使用 MVA-5T4 时的预期进展率为 70%；单侧 5%显著性水平下 85%的功效。
共招募了 94 名符合条件的患者，中位年龄为 65 岁（范围 42-82），中位随访时间为 34 个月（范围 2-46）。总体而言，59 名患者接受了 MVA-5T4 治疗，35 名患者接受了安慰剂治疗。接受 MVA-5T4 治疗的患者中位数接受的 MVA-5T4 注射次数为 7 次（范围 0-9 次），而接受安慰剂治疗的患者中位数为 6 次（范围 1-12 次）。两组的中位无进展生存期相同（3.0 个月）。两组的 25 周进展率相似：接受 MVA-5T4 治疗的患者为 80.0%，接受安慰剂治疗的患者为 85.7%（风险差异-5.7%，95%CI-21.4%至 10.0%）。接受 MVA-5T4 治疗的患者中位临床干预时间有所改善：7.6 个月（范围 6.7-9.5）vs. 5.6 个月（范围 4.9-7.6）。
在无症状复发的患者中接种 MVA-5T4 耐受性良好，但在 25 周时并未提高进展率。接受 MVA-5T4 治疗的大多数患者比接受安慰剂治疗的患者临床干预时间晚。
NCT01556841。
