既往曲妥珠单抗联合甲磺酸埃瑞布林加曲妥珠单抗作为人表皮生长因子受体2阳性局部复发或转移性乳腺癌一线治疗的临床效果:一项II期、单组、多中心研究的结果

IF 3.3 4区 医学 Q2 ONCOLOGY
S. Puhalla, S. Wilks, A. Brufsky, Joyce O’Shaughnessy, L. Schwartzberg, E. Berrak, James Song, L. Vahdat
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引用次数: 1

摘要

甲磺酸埃瑞布林是一种新型的非紫杉烷微管动力学抑制剂,属于软海绵素类抗肿瘤药物,适用于既往接受过2次以上化疗方案的转移性乳腺癌患者。在人类表皮生长因子受体2阳性患者中,伊瑞布林加曲妥珠单抗一线联合治疗的II期试验的主要数据显示,71%的客观缓解率和耐受性与这些药物的已知特征一致。在这里,我们基于先前的曲妥珠单抗使用,对该联合治疗的疗效进行了预先指定的分析。患者在每21天周期的第1天和第8天静脉注射甲磺酸埃瑞布林1.4 mg/m2(相当于1.23 mg/m2埃瑞布林[以游离碱表示])加曲妥珠单抗(静脉注射8mg /kg /cycle 1,然后是6mg /kg)。客观缓解率、无进展生存期和耐受性在接受过或未接受过曲妥珠单抗辅助或新辅助(neo/adjuvant)治疗的患者中进行评估。52例患者(中位年龄:59.5岁)接受了伊瑞布林/曲妥珠单抗治疗,中位治疗持续时间约为31周;40.4% (n=21)的患者在接受艾瑞布林加曲妥珠单抗治疗转移性疾病之前曾接受过新/辅助曲妥珠单抗治疗(新/辅助治疗和研究治疗之间的中位时间:23个月)。trastuzumab-naïve患者(n=31)与先前接受曲妥珠单抗的患者相比,客观缓解率分别为77.4%和61.9%;反应持续时间分别为11.8个月和9.5个月;临床获益率分别为87.1%和81.0%;中位无进展生存期分别为12.2个月和11.5个月。在先前接受曲妥珠单抗与曲妥珠单抗naïve治疗的患者中,最常见的3/4级治疗出现的不良事件(发生在≥5%的患者中)分别是中性粒细胞减少(47.6%对32.3%)、周围神经病变(14.3%对25.8%)、发热性中性粒细胞减少(14.3%对3.2%)、疲劳(9.5%对6.5%)、恶心(9.5%对0%)、呕吐(9.5%对3.2%)和白细胞减少(9.5%对3.2%)。在人表皮生长因子受体2阳性转移性乳腺癌患者中,一线艾瑞布林/曲妥珠单抗治疗显示出显著的抗肿瘤活性,并且耐受性良好,无论先前是否接受过新/辅助曲妥珠单抗治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Clinical effects of prior trastuzumab on combination eribulin mesylate plus trastuzumab as first-line treatment for human epidermal growth factor receptor 2 positive locally recurrent or metastatic breast cancer: results from a Phase II, single-arm, multicenter study
Eribulin mesylate, a novel nontaxane microtubule dynamics inhibitor in the halichondrin class of antineoplastic drugs, is indicated for the treatment of patients with metastatic breast cancer who previously received ≥2 chemotherapy regimens in the metastatic setting. Primary data from a Phase II trial for the first-line combination of eribulin plus trastuzumab in human epidermal growth factor receptor 2 positive patients showed a 71% objective response rate and tolerability consistent with the known profile of these agents. Here, we present prespecified analyses of efficacy of this combination based on prior trastuzumab use. Patients received eribulin mesylate 1.4 mg/m2 (equivalent to 1.23 mg/m2 eribulin [expressed as free base]) intravenously on days 1 and 8 plus trastuzumab (8 mg/kg intravenously/cycle 1, then 6 mg/kg) on day 1 of each 21-day cycle. Objective response rates, progression-free survival, and tolerability were assessed in patients who had and had not received prior adjuvant or neoadjuvant (neo/adjuvant) trastuzumab treatment. Fifty-two patients (median age: 59.5 years) received eribulin/trastuzumab for a median treatment duration of ~31 weeks; 40.4% (n=21) had been previously treated with neo/adjuvant trastuzumab prior to treatment with eribulin plus trastuzumab for metastatic disease (median time between neo/adjuvant and study treatment: 23 months). In trastuzumab-naïve patients (n=31) compared with those who had received prior trastuzumab, objective response rate was 77.4% versus 61.9%, respectively; duration of response was 11.8 versus 9.5 months, respectively; clinical benefit rate was 87.1% versus 81.0%, respectively; and median progression-free survival was 12.2 versus 11.5 months, respectively. The most common grade 3/4 treatment-emergent adverse events (occuring in ≥5% of patients) in patients who received prior trastuzumab versus trastuzumab naïve patients, respectively, were neutropenia (47.6% vs 32.3%), peripheral neuropathy (14.3% vs 25.8%), febrile neutropenia (14.3% vs 3.2%), fatigue (9.5% vs 6.5%), nausea (9.5% vs 0%), vomiting (9.5% vs 3.2%), and leukopenia (9.5% vs 3.2%). In patients with human epidermal growth factor receptor 2 positive metastatic breast cancer, first-line eribulin/trastuzumab treatment demonstrated substantial antitumor activity and was well tolerated, regardless of prior neo/adjuvant trastuzumab treatment.
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CiteScore
4.10
自引率
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40
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