背景:由于心脏毒性问题,表柔比星和曲妥珠单抗的同时使用尚未得到充分研究.这项研究旨在检查人表皮生长因子受体2(HER2)阳性早期乳腺癌(EBC)患者的心脏毒性和病理完全缓解(pCR)率。
方法:我们在NCBI/PubMed中对相关文献进行了系统的搜索,Cochrane数据库,2000年1月1日至2021年2月28日的II期或III期随机对照试验的国际会议摘要,重点是HER2阳性EBC患者的并行治疗方案。为了比较心脏毒性的风险和pCR率的几率,我们进行了线性meta回归分析,以研究多个协变量的影响.
结果:我们分析了7项新辅助试验,这些试验涉及表阿霉素和曲妥珠单抗与1797例患者的同时使用。使用的表柔比星的累积剂量中位数为300mg/m2,共报告了96次不良心脏事件。与非并行方案相比,并行方案并未导致心脏毒性的显着增加(风险比[RR]=1.18,95%置信区间[CI]=0.68-2.05)。与非同时或不含蒽环类药物的方案相比,同时治疗方案与pCR率显著增加相关(比值比=1.48,95%CI=1.04-2.12).线性固定效应荟萃回归分析表明,在包括更多激素受体阳性EBC患者的试验中,心脏毒性的RR随着治疗方案的同步而显着增加,pCR率变得不那么显著。
结论:曲妥珠单抗和低剂量表柔比星的组合对pCR率产生积极影响,而心脏毒性没有显著增加。我们建议探索HR阴性的并发治疗方案,HER2阳性肿瘤增强pCR率,由于潜在的心脏毒性,建议谨慎治疗HR阳性肿瘤。
BACKGROUND: Due to cardiotoxicity concerns, the concurrent use of epirubicin and trastuzumab has not been fully studied. This study aimed to examine the cardiotoxicity and pathological complete response (pCR) rate associated with the concurrent regimens in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer (EBC).
METHODS: We conducted a systematic search for relevant literature in the NCBI/PubMed, the Cochrane database, and international conference abstracts for phase II or III randomized controlled trials between January 1, 2000, and February 28, 2021, focusing on the concurrent regimens in patients with HER2-positive EBC. To compare the risk of cardiotoxicity and the odds of the pCR rate, we performed linear meta-regression analyses to investigate the effects of multiple covariates.
RESULTS: We analyzed 7 neoadjuvant trials involving the concurrent use of epirubicin and trastuzumab with 1797 patients. The median cumulative dose of epirubicin used was 300 mg/m2, with a total of 96 reported adverse cardiac events. The concurrent regimens did not result in a significant increase in cardiotoxicity compared to nonconcurrent regimens (risk ratio [RR] = 1.18, 95% confidence interval [CI] = 0.68-2.05). Compared with nonconcurrent or non-anthracycline-containing regimens, concurrent regimens were associated with a significant increase in the pCR rate (odds ratio = 1.48, 95% CI = 1.04-2.12). The linear fixed-effects meta-regression analysis indicated that in trials including more patients with hormone receptor-positive EBC, the RR of cardiotoxicity significantly increased with concurrent regimens, and the pCR rate became less significant.
CONCLUSIONS: The combination of trastuzumab and a low dose of epirubicin positively impacted the pCR rate without a significant increase in cardiotoxicity. We recommend exploring concurrent regimens for HR-negative, HER2-positive tumors to enhance pCR rates, with caution advised for HR-positive tumors due to potential cardiotoxicity.