曲妥珠单抗对比观察用于 HER2 无扩增早期乳腺癌伴循环肿瘤细胞（EORTC 90091-10093、BIG 1-12、Treat CTC）：一项随机 II 期试验。
Trastuzumab versus observation for HER2 nonamplified early breast cancer with circulating tumor cells (EORTC 90091-10093, BIG 1-12, Treat CTC): a randomized phase II trial.
机构信息
Department of Medical Oncology, Institut Jules Bordet, Universite ´ Libre de Bruxelles, Brussels, Belgium; Breast Cancer Translational Research Laboratory J. C. Heuson, Institut Jules Bordet, Universite ´ Libre de Bruxelles, Brussels, Belgium.
European Organization for Research and Treatment of Cancer (EORTC) Headquarters, Brussels, Belgium.
出版信息
Ann Oncol. 2018 Aug 1;29(8):1777-1783. doi: 10.1093/annonc/mdy211.
BACKGROUND
Trastuzumab improves the outcome of women with HER2 positive breast cancer. We aimed to assess whether trastuzumab decreases the detection rate of circulating tumor cells (CTCs) in women with high risk, HER2 nonamplified, early breast cancer.
PATIENTS AND METHODS
The EORTC 90091-10093 BIG 1-12 Treat CTC is a phase II trial, conducted in 70 hospitals and 6 CTC laboratories across 5 European countries. Patients with centrally confirmed HER2 nonamplified breast cancer and ≥1 centrally confirmed CTC per 15 ml of blood by CellSearch® following surgery and (neo)adjuvant chemotherapy were randomized (1 : 1) to 6 cycles of trastuzumab intravenously versus 18 weeks of observation. Randomization was stratified for center, locally confirmed estrogen receptor status and adjuvant versus neoadjuvant chemotherapy. The primary end point was rate of detection of ≥1 CTC per 15 ml of blood at week 18. Secondary end points were invasive disease-free survival (iDFS) and cardiac safety.
RESULTS
Between 30 April 2013 and 17 October 2016, 1317 patients were screened; 95 (7.2%) had detectable CTC(s), and 63 (4.8%) were randomized to trastuzumab (n = 31) or observation (n = 32). Fifty-eight patients were assessable for the primary end point, 29 in each arm. In 9 of the 58 patients, CTC(s) were still detected at week 18 : 5 in the trastuzumab and 4 in the observation arm (one-sided Fisher's exact test, P = 0.765). An Independent Data Monitoring Committee recommended stopping further accrual for futility for the primary end point. Median follow-up at database lock was 13 months (IQR 4-16.5). The 1-year iDFS was 93.8% (95% CI 77.3-98.4) in the observation versus 84.8% (95% CI 63.4-94.2) in the trastuzumab arm. No grade 2-4 cardiac events were observed in the trastuzumab arm.
CONCLUSION
Trastuzumab does not decrease the detection rate of CTCs in HER2 nonamplified, nonmetastatic breast cancer.
背景
曲妥珠单抗可改善 HER2 阳性乳腺癌患者的预后。我们旨在评估曲妥珠单抗是否会降低 HER2 无扩增、早期乳腺癌高危患者循环肿瘤细胞（CTC）的检出率。
患者和方法
EORTC 90091-10093 BIG 1-12 Treat CTC 是一项在 5 个欧洲国家的 70 家医院和 6 家 CTC 实验室开展的 II 期临床试验。入组患者为经中心确认的 HER2 无扩增乳腺癌，术后和（新）辅助化疗后，通过 CellSearch®检测每 15ml 血液中至少有 1 个经中心确认的 CTC。患者按 1：1 随机分配至接受 6 个周期静脉注射曲妥珠单抗或 18 周观察。随机分组按中心、局部确认的雌激素受体状态、辅助化疗与新辅助化疗进行分层。主要终点为第 18 周时每 15ml 血液中检出至少 1 个 CTC 的比例。次要终点为无侵袭性疾病生存（iDFS）和心脏安全性。
结果
2013 年 4 月 30 日至 2016 年 10 月 17 日，共筛选了 1317 例患者；其中 95 例（7.2%）检出了 CTC，63 例（4.8%）被随机分配至曲妥珠单抗组（n=31）或观察组（n=32）。63 例患者中有 58 例可评估主要终点，每组各 29 例。在 58 例可评估患者中，有 58 例（9 例在观察组，4 例在曲妥珠单抗组）在第 18 周仍检出 CTC（Fisher 确切概率单侧检验，P=0.765）。独立数据监测委员会建议因主要终点无效而停止进一步入组。数据锁定时的中位随访时间为 13 个月（IQR 4-16.5）。观察组的 1 年 iDFS 为 93.8%（95%CI 77.3-98.4），曲妥珠单抗组为 84.8%（95%CI 63.4-94.2）。曲妥珠单抗组未观察到 2-4 级心脏事件。
结论
在 HER2 无扩增、无转移的乳腺癌中，曲妥珠单抗并未降低 CTC 的检出率。
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