T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab
T-DM1 Activity in Metastatic Human Epidermal Growth Factor Receptor 2-Positive Breast Cancers That Received Prior Therapy With Trastuzumab and Pertuzumab
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DOI：
10.1200/jco.2016.67.3624
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发表时间：
2016-10-10
影响因子：
45.3
通讯作者：
Murthy, Rashmi
中科院分区：
文献类型：
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作者：
Dzimitrowicz, Hannah;Berger, Michael;Murthy, Rashmi
目的Ado-trastuzumab emtansine (T-DM1) 目前被批准用于治疗既往接受过曲妥珠单抗和紫杉烷治疗的人表皮生长因子受体 2 (HER2) 阳性转移性乳腺癌 (MBC) 患者。然而，尚无关于先前接受帕妥珠单抗治疗的患者中 T-DM1 活性的数据，帕妥珠单抗现已被纳入标准一线治疗。本研究的目的是评估 T-DM1 在既往接受曲妥珠单抗和帕妥珠单抗治疗的当代患者群体中的常规临床实践中的疗效。 患者和方法我们通过电子药房记录和部门数据库，确定了 2013 年 3 月 1 日至 2015 年 7 月 15 日期间接受曲妥珠单抗和帕妥珠单抗后接受 T-DM1 的所有 HER2 阳性 MBC 患者。 机构：MD 安德森癌症中心、耶鲁大学斯米洛癌症医院和俄亥俄州立大学詹姆斯癌症医院。我们审查了每个病例的医疗记录，以确认治疗顺序和结果。结果 在患者中，82 名患者被识别，78 名可用于结果分析； 32% 的人接受 T-DM1 作为一线和二线治疗，48% 的人接受四线或更晚的治疗。治疗持续时间延长（定义为治疗6个月）的比率为30.8%（95% CI，20.6%至41.1%），肿瘤缓解率为17.9%（95% CI，9.4%至26.4%）。中位治疗持续时间为 4.0 个月（95% CI，2.7 至 5.1；范围，0 至 22.5 个月）。 84% 的患者因疾病进展而停用 T-DM1，10% 的患者因毒性而停用。结论肿瘤缓解率低于先前报告的曲妥珠单抗耐药、HER2 阳性 MBC，但三分之一的患者接受 T-DM1 治疗 6 个月，这表明先前接受帕妥珠单抗的患者具有临床相关获益。
PurposeAdo-trastuzumab emtansine (T-DM1) is currently approved for treatment in patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (MBC) who previously received trastuzumab and a taxane. However, there are no data on the activity of T-DM1 in patients who received prior pertuzumab, which is now included as standard first-line therapy. The goal of this study was to assess the efficacy of T-DM1 in routine clinical practice in a contemporary patient population that received both prior trastuzumab and pertuzumab.Patients and MethodsWe identified all patients with HER2-positive MBC who received T-DM1 after trastuzumab and pertuzumab between March 1, 2013, and July 15, 2015, via electronic pharmacy records and departmental databases at three institutions: MD Anderson Cancer Center, Smilow Cancer Hospital at Yale, and The James Cancer Hospital at the Ohio State University. We reviewed medical records of each case to confirm treatment sequencing and outcome.ResultsOf patients, 82 were identified and 78 were available for outcome analysis; 32% received T-DM1 as first- and second-line line therapy, and 48% received it as fourth-line treatment or later. Rate of prolonged duration on therapy, defined as duration on therapy 6 months, was 30.8% (95% CI, 20.6% to 41.1%), and tumor response rate was 17.9% (95% CI, 9.4% to 26.4%). Median duration on therapy was 4.0 months (95% CI, 2.7 to 5.1; range, 0 to 22.5 months). T-DM1 was discontinued for disease progression in 84% of patients and for toxicity in 10%.ConclusionTumor response rates were lower than in prior reports of trastuzumab-resistant, HER2-positive MBC, but one third of patients received therapy with T-DM1 for 6 months, which suggests a clinically relevant benefit in patients who received prior pertuzumab.