TG4010 治疗性疫苗联合一线化疗治疗晚期非小细胞肺癌：一项对照 2B 期试验。
Therapeutic vaccination with TG4010 and first-line chemotherapy in advanced non-small-cell lung cancer: a controlled phase 2B trial.
机构信息
Hôpitaux Universitaires, Université de Strasbourg, Strasbourg, France.
出版信息
Lancet Oncol. 2011 Nov;12(12):1125-33. doi: 10.1016/S1470-2045(11)70259-5. Epub 2011 Oct 21.
BACKGROUND
Chemotherapy is the standard of care for advanced stages of non-small-cell lung cancer (NSCLC). TG4010 is a targeted immunotherapy based on a poxvirus (modified vaccinia virus Ankara) that codes for MUC1 tumour-associated antigen and interleukin 2. This study assessed TG4010 in combination with first-line chemotherapy in advanced NSCLC.
METHODS
148 patients with advanced (stage IIIB [wet] or IV) NSCLC expressing MUC1 by immunohistochemistry, and with performance status 0 or 1, were enrolled in parallel groups in this open-label, phase 2B study. 74 patients were allocated to the combination therapy group, and received TG4010 (10(8) plaque forming units) plus cisplatin (75 mg/m(2) on day 1) and gemcitabine (1250 mg/m(2) on days 1 and 8) repeated every 3 weeks for up to six cycles. 74 patients allocated to the control group received the same chemotherapy alone. Patients were allocated using a dynamic minimisation procedure stratified by centre, performance status, and disease stage. The primary endpoint was 6-month progression-free survival (PFS), with a target rate of 40% or higher in the experimental group. Analyses were done on an intention-to-treat basis. This study is completed and is registered with ClinicalTrials.gov, number NCT00415818.
FINDINGS
6-month PFS was 43·2% (32 of 74; 95% CI 33·4-53·5) in the TG4010 plus chemotherapy group, and 35·1% (26 of 74; 25·9-45·3) in the chemotherapy alone group. Fever, abdominal pain, and injection-site pain of any grade according to National Cancer Institute Common Toxicity Criteria were more common in the TG4010 group than in the chemotherapy alone group: 17 of 73 patients (23·3%) versus six of 72 (8·3%), 12 (16·4%) versus two (2·8%), and four (5·5%) versus zero (0%), respectively. The most common grade 3-4 adverse events were neutropenia (33 [45·2%] of patients in the TG4010 plus chemotherapy group vs 31 [43·1%] in the chemotherapy alone group) and fatigue (18 [24·7%] vs 13 [18·1%]); the only grade 3-4 events that differed significantly between groups were anorexia (three [4·1%] vs 10 [13·9%]) and pleural effusion (none vs four [5·6%]). 38 of 73 patients (52·1%) in the TG4010 plus chemotherapy group and 34 of 72 (47·2%) in the chemotherapy alone group had at least one serious adverse event.
INTERPRETATION
This phase 2B study suggests that TG4010 enhances the effect of chemotherapy in advanced NSCLC. A confirmatory phase 2B-3 trial has been initiated.
FUNDING
Transgene SA, Advanced Diagnostics for New Therapeutic Approaches (ADNA)/OSEO.
背景
化疗是治疗非小细胞肺癌（NSCLC）晚期的标准治疗方法。TG4010 是一种靶向免疫疗法，基于一种编码 MUC1 肿瘤相关抗原和白细胞介素 2 的痘病毒（改良安卡拉牛痘病毒）。这项研究评估了 TG4010 联合一线化疗治疗晚期 NSCLC 的疗效。
方法
本研究为开放标签、2B 期临床试验，共纳入 148 例晚期（IIIb 期[湿型]或 IV 期）MUC1 免疫组织化学阳性、体力状态 0 或 1 的 NSCLC 患者，按平行组分组。74 例患者被分配到联合治疗组，接受 TG4010（10(8) 空斑形成单位）联合顺铂（第 1 天 75mg/m(2)）和吉西他滨（第 1 天和第 8 天 1250mg/m(2)），每 3 周重复 6 个周期。74 例分配到对照组的患者单独接受相同的化疗。患者按中心、体力状态和疾病阶段进行动态最小化分层分配。主要终点是 6 个月无进展生存期（PFS），实验组目标率为 40%或更高。分析采用意向治疗。本研究已完成，并在 ClinicalTrials.gov 注册，编号为 NCT00415818。
结果
在 TG4010 联合化疗组中，6 个月 PFS 为 43.2%（32/74；95%CI 33.4-53.5），而单独化疗组为 35.1%（26/74；25.9-45.3）。根据国家癌症研究所常见毒性标准，发热、腹痛和任何级别的注射部位疼痛在 TG4010 组比单独化疗组更常见：73 例患者中有 17 例（23.3%）比 72 例中有 6 例（8.3%），12 例（16.4%）比 2 例（2.8%），4 例（5.5%）比 0 例（0%）。最常见的 3-4 级不良事件是中性粒细胞减少症（TG4010 联合化疗组 33 例[45.2%]与单独化疗组 31 例[43.1%]）和疲劳（18 例[24.7%]与 13 例[18.1%]）；两组唯一显著差异的 3-4 级事件是厌食症（3 例[4.1%]与 10 例[13.9%]）和胸腔积液（无 vs 4 例[5.6%]）。TG4010 联合化疗组 73 例患者中有 38 例（52.1%）和单独化疗组 72 例患者中有 34 例（47.2%）至少有 1 次严重不良事件。
结论
这项 2B 期研究表明，TG4010 增强了化疗在晚期 NSCLC 中的疗效。一项确证性 2B-3 期试验已经启动。
资金
Transgene SA，新治疗方法的高级诊断学（ADNA）/OSEO。
Zotero 插件