Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence
Prospective, randomized, single-blinded, multi-center phase II trial of two HER2 peptide vaccines, GP2 and AE37, in breast cancer patients to prevent recurrence
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DOI：
10.1007/s10549-020-05638-x
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发表时间：
2020-04-22
影响因子：
3.8
通讯作者：
Peoples, George E.
中科院分区：
文献类型：
--
作者：
Brown, Tommy A., II;Mittendorf, Elizabeth A.;Peoples, George E.
目的AE 37和GP 2是HER 2衍生肽疫苗。AE 37主要激发针对HER 2抗原的CD 4+应答，而GP 2激发针对HER 2抗原的CD 8+应答。这些肽在一项大型随机试验中进行了测试，以评估其预防表达HER 2的乳腺癌患者复发的能力。初步分析发现5年总体无病生存率（DFS）无差异，但亚组可能获益。在这里，我们提出了最终的里程碑分析。方法在这项4臂、前瞻性、随机、单盲、多中心的II期试验中，纳入了接受标准治疗后无病淋巴结阳性和高危淋巴结阴性的乳腺癌患者。疫苗（VG）与对照（CG）的6个月接种作为主要疫苗系列，每6个月间隔4次加强接种。对人口统计学、安全性、免疫学和DFS数据进行了评价。结果共入组456例患者; AE 37组VG组154例，CG组147例; GP 2组VG组89例，CG组91例。AE 37组的DFS与CG组相比无差异，但预先规定的探索性亚组分析显示晚期患者有获益趋势（p = 0.132，HR 0.573 CI 0.275-1.193），HER 2表达不足（p = 0.181，HR 0.756 CI 0.499-1.145）和三阴性乳腺癌（p = 0.266，HR 0.443 CI 0.114-1.717）。在HER 2低表达和晚期患者中，与CG相比，VG（p = 0.039，HR 0.375 CI 0.142-0.988）具有显著获益。与CG相比，GP 2组的DFS无显著差异，但在亚组分析中，与CG相比，VG中的HER 2阳性患者无复发，且DFS有改善的趋势（p = 0.052）。结论AE 37和GP 2在某些乳腺癌患者亚组中是安全的，并可能与DFS的临床结局改善相关。根据这些发现，有必要根据乳腺癌患者的疾病生物学特征，对AE 37和GP 2疫苗联合和/或单独用于特定亚群的乳腺癌患者进行进一步评估。
Purpose AE37 and GP2 are HER2 derived peptide vaccines. AE37 primarily elicits a CD4+ response while GP2 elicits a CD8+ response against the HER2 antigen. These peptides were tested in a large randomized trial to assess their ability to prevent recurrence in HER2 expressing breast cancer patients. The primary analyses found no difference in 5-year overall disease-free survival (DFS) but possible benefit in subgroups. Here, we present the final landmark analysis. Methods In this 4-arm, prospective, randomized, single-blinded, multi-center phase II trial, disease-free node positive and high-risk node negative breast cancer patients enrolled after standard of care therapy. Six monthly inoculations of vaccine (VG) vs. control (CG) were given as the primary vaccine series with 4 boosters at 6-month intervals. Demographic, safety, immunologic, and DFS data were evaluated. Results 456 patients were enrolled; 154 patients in the VG and 147 in CG for AE37, 89 patients in the VG and 91 in CG for GP2. The AE37 arm had no difference in DFS as compared to CG, but pre-specified exploratory subgroup analyses showed a trend towards benefit in advanced stage (p = 0.132, HR 0.573 CI 0.275-1.193), HER2 under-expression (p = 0.181, HR 0.756 CI 0.499-1.145), and triple-negative breast cancer (p = 0.266, HR 0.443 CI 0.114-1.717). In patients with both HER2 under-expression and advanced stage, there was significant benefit in the VG (p = 0.039, HR 0.375 CI 0.142-0.988) as compared to CG. The GP2 arm had no significant difference in DFS as compared to CG, but on subgroup analysis, HER2 positive patients had no recurrences with a trend toward improved DFS (p = 0.052) in VG as compared to CG. Conclusions This phase II trial reveals that AE37 and GP2 are safe and possibly associated with improved clinical outcomes of DFS in certain subgroups of breast cancer patients. With these findings, further evaluations are warranted of AE37 and GP2 vaccines given in combination and/or separately for specific subsets of breast cancer patients based on their disease biology.