Mates M, Fletcher G G, Freedman O C, Eisen A, Gandhi S, Trudeau M E, Dent S F
Cancer Centre of Southeastern Ontario, Kinston General Hospital; and Queen's University, Kingston, ON.
Program in Evidence-Based Care, Cancer Care Ontario; and Department of Oncology, McMaster University, Hamilton, ON.
Curr Oncol. 2015 Mar;22(Suppl 1):S114-22. doi: 10.3747/co.22.2322.
This systematic review addresses the question "What is the optimal targeted therapy for female patients with early-stage human epidermal growth factor receptor 2 (her2)-positive breast cancer?"
The medline and embase databases were searched for the period January 2008 to May 2014. The Standards and Guidelines Evidence directory of cancer guidelines and the Web sites of major guideline organizations were also searched.
Sixty publications relevant to the targeted therapy portion of the systematic review were identified. In four major trials (hera, National Surgical Adjuvant Breast and Bowel Project B-31, North Central Cancer Treatment Group N9831, and Breast Cancer International Research Group 006), adjuvant trastuzumab for 1 year was superior in disease-free survival (dfs) and overall survival (os) to no trastuzumab; trastuzumab showed no benefit in one trial (pacs 04). A shorter duration of trastuzumab (less than 1 year compared with 1 year) was evaluated, with mixed results for dfs: one trial showed superiority (finher), one trial could not demonstrate noninferiority (phare), another trial showed equivalent results (E 2198), and one trial is still ongoing (persephone). Longer trastuzumab duration (hera: 2 years vs. 1 year) showed no improvement in dfs or os and a higher rate of cardiac events. Newer her2-targeted agents (lapatinib, pertuzumab, T-DM1, neratinib) have been or are still being evaluated in both adjuvant and neoadjuvant trials, either by direct comparison with trastuzumab alone or combined with trastuzumab. In the neoadjuvant setting (neoaltto, GeparQuinto, Neosphere), trastuzumab alone or in combination with another anti-her2 agent (lapatinib, pertuzumab) was compared with either lapatinib or pertuzumab alone and showed superior or equivalent rates of pathologic complete response. In the adjuvant setting, lapatinib alone or in combination with trastuzumab, compared with trastuzumab alone (altto) or with placebo (teach), was not superior in dfs. The results of the completed aphinity trial, evaluating the role of dual her2 blockade with trastuzumab and pertuzumab, are highly anticipated. Ongoing trials are evaluating trastuzumab as a single agent without adjuvant chemotherapy (respect) and in patients with low her2 expression (National Surgical Adjuvant Breast and Bowel Project B-47).
Taking into consideration disease characteristics and patient preference, 1 year of trastuzumab should be offered to all patients with her2-positive breast cancer who are receiving adjuvant chemotherapy. Cardiac function should be regularly assessed in this patient population.
本系统评价探讨“早期人表皮生长因子受体2（HER2）阳性乳腺癌女性患者的最佳靶向治疗方案是什么？”这一问题。
检索了2008年1月至2014年5月期间的Medline和Embase数据库。还检索了癌症指南的标准与指南证据目录以及主要指南组织的网站。
共识别出60篇与该系统评价靶向治疗部分相关的文献。在四项主要试验（HERA、国家外科辅助乳腺和肠道项目B-31、北中部癌症治疗组N9831以及乳腺癌国际研究组006）中，辅助使用曲妥珠单抗1年在无病生存期（DFS）和总生存期（OS）方面优于不使用曲妥珠单抗；在一项试验（PACS 04）中曲妥珠单抗未显示出益处。对较短疗程的曲妥珠单抗（与1年相比少于1年）进行了评估，DFS结果不一：一项试验显示有优势（FINHER），一项试验未能证明非劣效性（PHARE），另一项试验显示结果相当（E 2198），还有一项试验仍在进行中（珀尔塞福涅）。更长疗程的曲妥珠单抗（HERA：2年对比1年）在DFS或OS方面未显示出改善，且心脏事件发生率更高。新型HER2靶向药物（拉帕替尼、帕妥珠单抗、T-DM1、来那替尼）已在辅助和新辅助试验中进行或仍在进行评估，要么直接与单独使用曲妥珠单抗比较，要么与曲妥珠单抗联合使用。在新辅助治疗中（NEOALTTO、GeparQuinto、Neosphere），单独使用曲妥珠单抗或与另一种抗HER2药物（拉帕替尼、帕妥珠单抗）联合使用，与单独使用拉帕替尼或帕妥珠单抗进行比较，显示出更高或相当的病理完全缓解率。在辅助治疗中，单独使用拉帕替尼或与曲妥珠单抗联合使用，与单独使用曲妥珠单抗（ALTTO）或与安慰剂（TEACH）相比，在DFS方面并不更优。正在进行的APHINITY试验评估曲妥珠单抗和帕妥珠单抗双重HER2阻断作用的结果备受期待。正在进行的试验正在评估曲妥珠单抗作为单药不联合辅助化疗（RESPECT）以及在HER2低表达患者中的应用（国家外科辅助乳腺和肠道项目B-47）。
考虑到疾病特征和患者偏好，应向所有接受辅助化疗的HER2阳性乳腺癌患者提供1年的曲妥珠单抗治疗。应定期评估该患者群体的心脏功能。
