Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02.
Clinical trial results of the HER-2/neu (E75) vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02.
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DOI：
10.1002/cncr.26574
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发表时间：
2012-05-15
期刊：
影响因子：
6.2
通讯作者：
Peoples GE
中科院分区：
文献类型：
--
作者：
Mittendorf EA;Clifton GT;Holmes JP;Clive KS;Patil R;Benavides LC;Gates JD;Sears AK;Stojadinovic A;Ponniah S;Peoples GE
作者用人类白细胞抗原(HLAA2/A3)限制性HER-2/neu(HER2)多肽和粒细胞-巨噬细胞集落刺激因子E75免疫乳腺癌患者进行了探索性的1-2期临床试验。疫苗是作为辅助治疗给予的，以防止疾病复发。他们此前曾报道，该疫苗在刺激E75特异性细胞毒T细胞的扩张方面是安全有效的。在这里，他们报告了对无病生存(DFS)的24个月里程碑式的分析。这些剂量升级/计划优化试验纳入了HER2(免疫组织化学[IHC]1-3+)表达肿瘤的淋巴结阳性和高危淋巴结阴性患者。对HL A-A2/A3+患者接种疫苗；对其他患者进行前瞻性随访，作为复发控制。DFS采用Kaplan-Meier曲线分析，组间比较采用对数等级检验。在195名登记的患者中，182人可评估：接种疫苗组106人(58.2%)，对照组76人(41.8%)。24个月标志性分析DFS，接种组为94.3%，对照组为86.8%(P=0.08)。重要的是，由于试验设计，65%的患者接种的疫苗剂量低于最佳剂量。在亚组分析中，从疫苗接种中获益最多的患者(接种组和对照组)有淋巴结阳性(DFS，90.2%比79.1%；P=.13)、HER2 IHC 1+-2+(DFS，94.0%比79.4%；P=.04)或1级或2级(DFS，98.4%比86.0%；P=.01)的肿瘤，并获得了最佳剂量(DFS，97.3%比86.8%；P=.08)。已经启动了加强接种计划；接受加强接种的患者没有复发。E75疫苗的临床疗效在某些患者中更为突出。3期试验招募HER2低表达肿瘤的淋巴结阳性患者是有必要的。
The authors conducted exploratory phase 1–2 clinical trials vaccinating breast cancer patients with E75, a human leukocyte antigen (HLA) A2/A3–restricted HER-2/neu (HER2) peptide, and granulocyte-macrophage colony-stimulating factor. The vaccine is given as adjuvant therapy to prevent disease recurrence. They previously reported that the vaccine is safe and effective in stimulating expansion of E75-specific cytotoxic T cells. Here, they report 24-month landmark analyses of disease-free survival (DFS). These dose escalation/schedule optimization trials enrolled lymph node-positive and high-risk lymph node-negative patients with HER2 (immunohistochemistry [IHC] 1-3+) expressing tumors. HLA-A2/A3+ patients were vaccinated; others were followed prospectively as controls for recurrence. DFS was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests. Of 195 enrolled patients, 182 were evaluable: 106 (58.2%) in the vaccinated group and 76 (41.8%) in the control group. The 24-month landmark analysis DFS was 94.3% in the vaccinated group and 86.8% in the control group (P = .08). Importantly, because of trial design, 65% of patients received a lower than optimal vaccine dose. In subset analyses, patients who benefited most from vaccination (vaccinated group vs control group) had lymph node-positive (DFS, 90.2% vs 79.1%; P = .13), HER2 IHC 1+-2+ (DFS, 94.0% vs 79.4%; P = .04), or grade 1 or 2 (DFS, 98.4% vs 86.0%; P = .01) tumors and were optimally dosed (DFS, 97.3% vs 86.8%; P = .08). A booster program has been initiated; no patients receiving booster inoculations have recurred. The E75 vaccine has clinical efficacy that is more prominent in certain patients. A phase 3 trial enrolling lymph node-positive patients with HER2 low-expressing tumors is warranted.
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