Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Cancer. 2012 May 15;118(10):2594-602. doi: 10.1002/cncr.26574. Epub 2011 Oct 11.
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.
作者进行了探索性的 1-2 期临床试验，为乳腺癌患者接种 E75，这是一种人类白细胞抗原（HLA）A2/A3 限制性 HER-2/neu（HER2）肽和粒细胞-巨噬细胞集落刺激因子。该疫苗作为辅助疗法用于预防疾病复发。他们之前报告说，该疫苗在刺激 E75 特异性细胞毒性 T 细胞的扩增方面是安全有效的。在这里，他们报告了无病生存（DFS）的 24 个月里程碑分析。
这些剂量递增/方案优化试验招募了淋巴结阳性和高风险淋巴结阴性的 HER2（免疫组织化学[IHC] 1-3（+））表达肿瘤患者。HLA-A2/A3（+）患者接种疫苗；其他人作为复发的对照进行前瞻性随访。通过 Kaplan-Meier 曲线分析 DFS；使用对数秩检验比较组。
在 195 名入组患者中，182 名可评估：接种组 106 名（58.2%），对照组 76 名（41.8%）。接种组 24 个月的里程碑分析 DFS 为 94.3%，对照组为 86.8%（P =.08）。重要的是，由于试验设计，65%的患者接受了低于最佳剂量的疫苗。在亚组分析中，从疫苗接种中受益最大的患者（接种组与对照组）具有淋巴结阳性（DFS，90.2%对 79.1%；P =.13）、HER2 IHC 1+-2+（DFS，94.0%对 79.4%；P =.04）或 1 级或 2 级（DFS，98.4%对 86.0%；P =.01）肿瘤和最佳剂量（DFS，97.3%对 86.8%；P =.08）。已经启动了一个加强计划；接受加强接种的患者均未复发。
E75 疫苗具有临床疗效，在某些患者中更为明显。有必要招募淋巴结阳性且 HER2 低表达肿瘤的患者进行 3 期试验。
