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曲妥珠单抗emtansine治疗HER2阳性转移性乳腺癌安全有效

  1. 曲妥珠单抗

来源:J Clin Oncol 2013-02-08 09:35

曲妥珠单抗emtansine(T-DM1)是一种抗体-药物偶联物,该药由细胞毒类药物DM1通过稳定的硫醚链接基团缀合于曲妥珠单抗而成,之前的单组研究表明该药具有临床活性,这些研究的主要招募对象为人表皮生长因子受体2(HER2)呈阳性的转移性乳腺癌(MBC)患者,在对这些出现转移的患者进行以HER2为靶点的治疗过程中,患者病情均出现进展。

曲妥珠单抗emtansine(T-DM1)是一种抗体-药物偶联物,该药由细胞毒类药物DM1通过稳定的硫醚链接基团缀合于曲妥珠单抗而成,之前的单组研究表明该药具有临床活性,这些研究的主要招募对象为人表皮生长因子受体2(HER2)呈阳性的转移性乳腺癌(MBC)患者,在对这些出现转移的患者进行以HER2为靶点的治疗过程中,患者病情均出现进展。在2013年2月4日在线出版的《临床肿瘤学杂志》(Journal of Clinical Oncology)上,美国梅奥诊所的Edith A. Perez博士等人又发表了该药的一项临床II期随机研究结果,该研究结果表明,与HT相比,T-DM1一线治疗HER2呈阳性的转移性乳腺癌患者时,可显著改善患者的无进展生存时间,并且具有良好的安全性。

在研究过程中,HER2 呈阳性的转移性乳腺癌或复发性局部晚期乳腺癌患者(N = 137)经随机分组,分别接受曲妥珠单抗联合多西他赛(HT; n = 70)或T-DM1 (n = 67)一线治疗,直至出现病情进展或毒性无法耐受。该研究主要终点为研究者评估的患者无进展生存时间(PFS)及安全性。关键的几项次要终点包括整体生存时间(OS)、客观缓解率(ORR)、客观缓解维持时间、临床获益率以及生活质量。

研究结果显示,HT组患者的中位无进展生存时间(PFS)为9.2个月,T-DM1患者为14.2个月(风险比, 0.59; 95% CI, 0.36 至 0.97);两组患者的中位随访时间约为14个月。HT组患者客观缓解率(ORR)为58.0% (95% CI, 45.5% 至 69.2%),T-DM1患者为64.2% (95% CI, 51.8%至74.8%)。与HT 相比,T-DM1的安全性较好,≥ 3级不良事件(AE)较少(46.4% VS 90.9%),同时因不良事件而中止治疗的现象(7.2% v 40.9%)及严重不良事件(20.3% v 25.8%)也较少。两治疗组的整体生存时间(OS)初步结果类似;两组患者的中位随访时间约23个月。(生物谷Bioon.com)

相关文献

Phase II Randomized Study of Trastuzumab Emtansine Versus Trastuzumab Plus Docetaxel in Patients With Human Epidermal Growth Factor Receptor 2-Postive Metastatic Breast Cancer.

J Clin Oncol 2013 :

Hurvitz SA Dirix L Kocsis J Bianchi GV Lu J Vinholes J Guardino E Song C Tong B Ng V Chu YW Perez EA

Sara A. Hurvitz, University of California at Los Angeles Jonsson Comprehensive Cancer Center and Translational Oncology Research International, Los Angeles, CA; Luc Dirix, Sint-Augustinus Hospital, Antwerp, Belgium; Judit Kocsis, Semmelweis University Hospital, Budapest, Hungary; Giulia V. Bianchi, Fondazione Istituto Di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy; Janice Lu, State University of New York at Stony Brook, Stony Brook, NY; Jeferson Vinholes, Clinica de Oncologia, Porto Alegre, Brazil; Ellie Guardino, Chunyan Song, Barbara Tong, Vivian Ng, and Yu-Waye Chu, Genentech, South San Francisco, CA; and Edith A. Perez, Mayo Clinic, Jacksonville, FL.

PURPOSETrastuzumab emtansine (T-DM1), an antibody-drug conjugate composed of the cytotoxic agent DM1 conjugated to trastuzumab via a stable thioether linker, has shown clinical activity in single-arm studies enrolling patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (MBC) whose disease had progressed on HER2-targeted therapy in the metastatic setting.Patients And METHODSPatients (N = 137) with HER2-positive MBC or recurrent locally advanced breast cancer were randomly assigned to trastuzumab plus docetaxel (HT; n = 70) or T-DM1 (n = 67) as first-line treatment until disease progression or unacceptable toxicity. Primary end points were investigator-assessed progression-free survival (PFS) and safety. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of objective response, clinical benefit rate, and quality of life.ResultsMedian PFS was 9.2 months with HT and 14.2 months with T-DM1 (hazard ratio, 0.59; 95% CI, 0.36 to 0.97); median follow-up was approximately 14 months in both arms. ORR was 58.0% (95% CI, 45.5% to 69.2%) with HT and 64.2% (95% CI, 51.8% to 74.8%) with T-DM1. T-DM1 had a favorable safety profile versus HT, with fewer grade ≥ 3 adverse events (AEs; 46.4% v 90.9%), AEs leading to treatment discontinuations (7.2% v 40.9%), and serious AEs (20.3% v 25.8%). Preliminary OS results were similar between treatment arms; median follow-up was approximately 23 months in both arms. CONCLUSIONIn this randomized phase II study, first-line treatment with T-DM1 for patients with HER2-positive MBC provided a significant improvement in PFS, with a favorable safety profile, versus HT.

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