Mittendorf E A, Clifton G T, Holmes J P, Schneble E, van Echo D, Ponniah S, Peoples G E
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston.
Blanchfield Army Community Hospital, Fort Campbell.
Ann Oncol. 2014 Sep;25(9):1735-1742. doi: 10.1093/annonc/mdu211. Epub 2014 Jun 6.
E75 (nelipepimut-S) is a human leukocyte antigen (HLA)-A2/A3-restricted immunogenic peptide derived from the HER2 protein. We have conducted phase I/II clinical trials vaccinating breast cancer patients with nelipepimut-S and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the adjuvant setting to prevent disease recurrence. All patients have completed 60 months follow-up, and here, we report the final analyses.
The studies were conducted as dose escalation/schedule optimization trials enrolling node-positive and high-risk node-negative patients with tumors expressing any degree of HER2 (immunohistochemistry 1-3+). HLA-A2/3+ patients were vaccinated; others were followed prospectively as controls. Local and systemic toxicity was monitored. Clinical recurrences were documented, and disease-free survival (DFS) was analyzed by Kaplan-Meier curves; groups were compared using log-rank tests.
Of 195 enrolled patients, 187 were assessable: 108 (57.8%) in the vaccinated group (VG) and 79 (42.2%) in the control group (CG). The groups were well matched for clinicopathologic characteristics. Toxicities were minimal. Five-year DFS was 89.7% in the VG versus 80.2% in the CG (P = 0.08). Due to trial design, 65% of patients received less than the optimal vaccine dose. Five-year DFS was 94.6% in optimally dosed patients (P = 0.05 versus the CG) and 87.1% in suboptimally dosed patients. A voluntary booster program was initiated, and among the 21 patients that were optimally boosted, there was only one recurrence (DFS = 95.2%).
The E75 vaccine is safe and appears to have clinical efficacy. A phase III trial evaluating the optimal dose and including booster inoculations has been initiated.
NCT00841399, NCT00584789.
E75（奈立肽）是一种源自HER2蛋白的人白细胞抗原（HLA）-A2/A3限制性免疫原性肽。我们开展了I/II期临床试验，在辅助治疗中用奈立肽和粒细胞巨噬细胞集落刺激因子（GM-CSF）对乳腺癌患者进行疫苗接种以预防疾病复发。所有患者均已完成60个月的随访，在此我们报告最终分析结果。
这些研究作为剂量递增/方案优化试验开展，纳入了肿瘤表达任何程度HER2（免疫组织化学1-3+）的淋巴结阳性和高危淋巴结阴性患者。对HLA-A2/3阳性患者进行疫苗接种；其他患者作为对照进行前瞻性随访。监测局部和全身毒性。记录临床复发情况，并通过Kaplan-Meier曲线分析无病生存期（DFS）；使用对数秩检验对组间进行比较。
195例入组患者中,187例可评估：疫苗接种组（VG）108例（57.8%），对照组（CG）79例（42.2%）。两组在临床病理特征方面匹配良好。毒性极小。VG组的5年DFS为89.7%，CG组为80.2%（P = 0.08）。由于试验设计，65%的患者接受的疫苗剂量低于最佳剂量。最佳剂量组患者的5年DFS为94.6%（与CG组相比，P = 0.05），次最佳剂量组为87.1%。启动了一项自愿加强免疫计划，在21例接受最佳加强免疫的患者中，仅有1例复发（DFS = 95.2%）。
E75疫苗安全且似乎具有临床疗效。已启动一项评估最佳剂量并包括加强接种的III期试验。
NCT00841399，NCT00584789。
