曲妥珠单抗-美坦新偶联物用于治疗残留浸润性 HER2 阳性乳腺癌。
Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.
机构信息
From the German Breast Group, Neu-Isenburg (G.M., S.L., H.H.F., P.W.), the Center for Hematology and Oncology Bethanien, Frankfurt (S.L.), the AGO-B and HELIOS Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), the Arbeitsgemeinschaft Gynäkologische Onkologie - Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), and Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg (P.W.) - all in Germany; the National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation and Orlando Health University of Florida Health Cancer Center, Orlando (E.P.M.); the NSABP Foundation and Allegheny Health Network Cancer Institute (N.W.) and the NSABP Foundation and University of Pittsburgh Cancer Institute, School of Medicine (P.R.), Pittsburgh; Hospital Universitario La Paz-Instituto de Investigación Hospital Universitario La Paz, Madrid (A.R.); Institut Régional du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier, France (W.J.); the NSABP Foundation and Providence Portland Medical Center, Portland, OR (A.K.C.); the National Cancer Institute, Mexico City (C.A.-S.); the NSABP Foundation and Stanford University School of Medicine, Stanford (I.L.W.), and Genentech, South San Francisco (L.H.L., D.T., M.S., S.M.S.) - both in California; Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the Ireland Cooperative Oncology Research Group, Dublin (J.P.C.); Fudan University Shanghai Cancer Center (Z.S.) and Roche (China) Holding (H.W.), Shanghai; the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy (E.R.C.); F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom (H.D.); and the NSABP Foundation and Virginia Commonwealth University Massey Cancer Center, Richmond (C.E.G.).
出版信息
N Engl J Med. 2019 Feb 14;380(7):617-628. doi: 10.1056/NEJMoa1814017. Epub 2018 Dec 5.
BACKGROUND
Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.
METHODS
We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab. Patients were randomly assigned to receive adjuvant T-DM1 or trastuzumab for 14 cycles. The primary end point was invasive disease-free survival (defined as freedom from ipsilateral invasive breast tumor recurrence, ipsilateral locoregional invasive breast cancer recurrence, contralateral invasive breast cancer, distant recurrence, or death from any cause).
RESULTS
At the interim analysis, among 1486 randomly assigned patients (743 in the T-DM1 group and 743 in the trastuzumab group), invasive disease or death had occurred in 91 patients in the T-DM1 group (12.2%) and 165 patients in the trastuzumab group (22.2%). The estimated percentage of patients who were free of invasive disease at 3 years was 88.3% in the T-DM1 group and 77.0% in the trastuzumab group. Invasive disease-free survival was significantly higher in the T-DM1 group than in the trastuzumab group (hazard ratio for invasive disease or death, 0.50; 95% confidence interval, 0.39 to 0.64; P<0.001). Distant recurrence as the first invasive-disease event occurred in 10.5% of patients in the T-DM1 group and 15.9% of those in the trastuzumab group. The safety data were consistent with the known safety profile of T-DM1, with more adverse events associated with T-DM1 than with trastuzumab alone.
CONCLUSIONS
Among patients with HER2-positive early breast cancer who had residual invasive disease after completion of neoadjuvant therapy, the risk of recurrence of invasive breast cancer or death was 50% lower with adjuvant T-DM1 than with trastuzumab alone. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472 .).
背景
接受新辅助化疗加人表皮生长因子受体 2（HER2）靶向治疗后仍有浸润性乳腺癌残留的患者预后较无残留癌者差。曲妥珠单抗-美坦新偶联物（T-DM1）是曲妥珠单抗与细胞毒药物美坦新（DM1，一种美登素衍生物和微管抑制剂）的抗体药物偶联物，在先前接受化疗加 HER2 靶向治疗的转移性乳腺癌患者中具有获益。
方法
我们进行了一项 3 期、开放性试验，纳入了接受新辅助治疗（包含紫杉烷[联合或不联合蒽环类药物]和曲妥珠单抗）后手术时乳房或腋窝仍有浸润性疾病的 HER2 阳性早期乳腺癌患者。患者被随机分配接受辅助 T-DM1 或曲妥珠单抗治疗 14 个周期。主要终点是无浸润性疾病生存（定义为同侧浸润性乳腺肿瘤复发、同侧局部区域浸润性乳腺癌复发、对侧浸润性乳腺癌、远处复发或任何原因死亡的无病生存）。
结果
在中期分析中，在 1486 例随机分配的患者中（T-DM1 组 743 例，曲妥珠单抗组 743 例），T-DM1 组有 91 例（12.2%）和曲妥珠单抗组有 165 例（22.2%）患者发生浸润性疾病或死亡。T-DM1 组 3 年时无浸润性疾病的患者比例为 88.3%，曲妥珠单抗组为 77.0%。T-DM1 组的无浸润性疾病生存显著高于曲妥珠单抗组（浸润性疾病或死亡的风险比，0.50；95%置信区间，0.39 至 0.64；P<0.001）。T-DM1 组远处复发作为首次浸润性疾病事件的发生率为 10.5%，而曲妥珠单抗组为 15.9%。安全性数据与 T-DM1 的已知安全性特征一致，与单独使用曲妥珠单抗相比，T-DM1 相关不良事件更多。
结论
在新辅助治疗后仍有浸润性疾病残留的 HER2 阳性早期乳腺癌患者中，与单独使用曲妥珠单抗相比，辅助 T-DM1 可使浸润性乳腺癌复发或死亡的风险降低 50%。（由 F. Hoffmann-La Roche/Genentech 资助；KATHERINE 临床试验.gov 编号，NCT01772472）。
Zotero 插件