预防肿瘤复发的疫苗在HER2过表达乳腺癌患者中显示出良好前景

2014年9月5日，旧金山讯。人类表皮生长因子受体2（HER2）过表达的乳腺癌女性患者或许能通过一种用于预防肿瘤复发的新型疫苗获益。一项有关该疫苗的II期试验的初级分析结果在上周五时公布于加利福尼亚州旧金山市举办的2014乳腺癌研讨会上。

得克萨斯州圣安东尼奥市圣安东尼奥军人医疗中心的Erika J. Schneble汇报了这项有关粒细胞巨噬细胞集落刺激因子（GM-CSF）联合GP2（一种来源于HER2的用以刺激CD8+T细胞识别HER2+肿瘤细胞的免疫原性肽）II期试验的初级分析结果。HER2是乳腺癌中常见的肿瘤相关抗原，是免疫治疗的一个新兴治疗靶点。

Dr. Schneble及其他研究人员完成了这项有关GP2疫苗预防乳腺癌复发的前瞻性、随机、多中心、II期临床试验项目，共计89例患者接受了疫苗接种；研究另外纳入了91例患者作为对照，仅接受了GM-CSF。

受试者们每月接种1次，持续接种6个月，之后接受每6个月一次共计4次的辅助给药。89例接种者和92例对照者在年龄、阳性淋巴结数量、肿瘤大小、分级、雌激素/黄体酮阳性率、或HER2表达水平方面不存在组间差异。

该疫苗和对照剂的毒性相当，提示疫苗的耐受性良好。仅有1例患者报告发生了3级局部和全身毒性反应。在34个月的中位随访期内，意向治疗人群和符合方案人群的无疾病存活率（DFS）相当。在HER2过度表达的肿瘤患者中（51例接种者和50例对照患者），意向治疗人群的DFS相当，在接种者中为94%，在对照受试者中为89%。在符合方案人群中，接种者的DFS达100%，而对照受试者为89%（P=0.08）。

Dr. Schneble总结道，GP2疫苗的安全性和耐受性良好。鉴于迄今为止符合方案人群中尚无复发病例，因而HER2过表达的肿瘤患者或能从中获得更大受益。Dr. Schneble向Practice Update透露：“这个结果很可能与联合使用了曲妥珠单抗有关，有待进行一项III期临床试验以评估疫苗与佐剂共同给药在HER2过表达女性患者中的应用。

September 5, 2014 – San Francisco – Women with breast cancer tumors that overexpress human epidermal growth factor receptor 2 (HER2) may benefit from a novel vaccine to prevent recurrence. Findings from a primary analysis of a phase 2 trial of this vaccine were presented Friday at the 2014 Breast Cancer Symposium, held in San Francisco, California, from September 4 – 6, 2014.

Erika J. Schneble, DO, of San Antonio Military Medical Center, San Antonio, Texas, presented a primary analysis of the phase 2 trial of granulocyte macrophage colony-stimulating factor (GM-CSF) plus GP2, a HER2-derived immunogenic peptide designed to stimulate CD8+T cells to recognize HER2+ tumor cells. Since HER2 is a commonly expressed tumor-associated antigen in breast cancer, it is an attractive target for immunotherapy.

Dr. Schneble and coinvestigators have completed accrual to their prospective, randomized, multicenter, phase 2 trial of the GP2 vaccine to prevent breast cancer recurrence. A total of 89 patients have been vaccinated and 91 patients are serving as controls, having received GM-CSF alone.

Subjects received six monthly inoculations followed by four boosters administered every 6 months. With 89 vaccinated and 91 control subjects enrolled and vaccinated, there are no differences between groups with respect to age, node positivity, tumor size, grade, estrogen/progesterone positivity, or HER2 expression.

The vaccine has been well tolerated with toxicities comparable between it and the control formulation. Only one grade 3 local and systemic toxicity reaction has been reported with the vaccine. At 34 (1 – 60) month median follow-up, disease-free survival (DFS) was comparable in the intent-to-treat and per-protocol populations. In patients whose tumors overexpress HER2 (51 vaccinated and 50 control patients), DFS in the intent-to-treat group was comparable at 94% in vaccinated and 89% in control subjects. In the per-protocol group, DFS was 100% in vaccinated, and 89% in control subjects (P = 0.08).

Dr. Schneble concluded that the GP2 vaccine is safe and well tolerated. Patients whose tumors overexpress HER2 may experience a potentially greater benefit, since to date no recurrences have occurred in this per-protocol group. Dr. Schneble told Practice Update that she attributes this possibility to synergism with trastuzumab therapy, which justifies a phase 3 trial evaluating the vaccine administered in the adjuvant setting to a population of women with HER2-overexpressing tumors.

Copyright © 2014 PracticeUpdate Editorial Team

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