曲妥珠单抗恩美曲妥珠单抗治疗残留HER2阳性乳腺癌的生存情况
Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.
作者信息
Geyer Charles E, Untch Michael, Huang Chiun-Sheng, Mano Max S, Mamounas Eleftherios P, Wolmark Norman, Rastogi Priya, Schneeweiss Andreas, Redondo Andres, Fischer Hans H, D'Hondt Véronique, Conlin Alison K, Guarneri Valentina, Wapnir Irene L, Jackisch Christian, Arce-Salinas Claudia, Fasching Peter A, DiGiovanna Michael P, Crown John P, Wuelfing Pia, Shao Zhimin, Rota Caremoli Elena, Bonnefoi Hervé R, Hennessy Bryan T, Stamatovic Ljiljana, Castro-Salguero Hugo, Brufsky Adam M, Knott Adam, Siddiqui Asna, Lambertini Chiara, Boulet Thomas, Nyawira Beatrice, Restuccia Eleonora, Loibl Sibylle
机构信息
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) - both in Pittsburgh; 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.), 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.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) - all in Germany; 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.); Orlando Health Cancer Institute, Orlando, FL (E.P.M.); Hospital Universitario La Paz-Instituto de Investigación del Hospital Universitario La Paz, Madrid (A.R.); L'Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier (V.D.), Institut Bergonié, INSERM Unité 1312, and Université de Bordeaux UFR Sciences Médicales, Bordeaux (H.R.B.) - all in France; Providence Cancer Institute, Portland, OR (A.K.C.); the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and Oncology 2, Istituto Oncologico Veneto IRCCS, Padua (V.G.), and the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo (E.R.C.) - all in Italy; Stanford University School of Medicine, Stanford, CA (I.L.W.); the National Cancer Institute, Mexico City (C.A.-S.); Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the All-Ireland Cooperative Oncology Research Group (J.P.C.), and the Oncology Unit, Cancer Clinical Trials and Research Unit, Beaumont RCSI Cancer Centre, and Cancer Trials Ireland (B.T.H.) - all in Dublin; Fudan University Shanghai Cancer Center, Shanghai, China (Z.S.); Institute for Oncology and Radiology of Serbia, Belgrade (L.S.); Grupo Médico Ángeles, Guatemala City, Guatemala (H.C.-S.); Roche Products, Welwyn Garden City, United Kingdom (A.K., A.S.); and F. Hoffmann-La Roche, Basel, Switzerland (C.L., T.B., B.N., E.R.).
出版信息
N Engl J Med. 2025 Jan 16;392(3):249-257. doi: 10.1056/NEJMoa2406070.
BACKGROUND
Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.
METHODS
We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles. Here, we report the prespecified final analysis of invasive disease-free survival and the second interim analysis of overall survival.
RESULTS
With a median follow-up of 8.4 years, T-DM1 sustained the improvement in invasive disease-free survival over trastuzumab (unstratified hazard ratio for invasive disease or death, 0.54; 95% confidence interval [CI], 0.44 to 0.66). Seven-year invasive disease-free survival was 80.8% with T-DM1 and 67.1% with trastuzumab (difference, 13.7 percentage points). T-DM1 also led to a significantly lower risk of death than trastuzumab (unstratified hazard ratio, 0.66; 95% CI, 0.51 to 0.87; P = 0.003). Seven-year overall survival was 89.1% with T-DM1 and 84.4% with trastuzumab (difference, 4.7 percentage points). Adverse events of grade 3 or higher were noted in 26.1% of the patients in the T-DM1 group and 15.7% of those in the trastuzumab group.
CONCLUSIONS
As compared with trastuzumab, T-DM1 improved overall survival with sustained improvement in invasive disease-free survival among patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant therapy. (Funded by F. Hoffmann-La Roche/Genentech; KATHERINE ClinicalTrials.gov number, NCT01772472.).
背景
人表皮生长因子受体2（HER2）阳性早期乳腺癌患者在新辅助全身治疗后仍有残余浸润性疾病，复发和死亡风险较高。一项3期开放标签试验KATHERINE的初步分析表明，与单独使用曲妥珠单抗相比，辅助使用曲妥珠单抗偶联物（T-DM1）可使浸润性乳腺癌或死亡风险降低50%。
方法
我们将在接受紫杉类化疗和曲妥珠单抗新辅助全身治疗后乳房或腋窝有残余浸润性疾病的HER2阳性早期乳腺癌患者随机分配，接受T-DM1或曲妥珠单抗治疗14个周期。在此，我们报告无浸润性疾病生存期的预先指定最终分析和总生存期的第二次中期分析。
结果
中位随访8.4年，T-DM1在无浸润性疾病生存期方面持续优于曲妥珠单抗（浸润性疾病或死亡的未分层风险比为0.54；95%置信区间[CI]为0.44至0.66）。T-DM1组7年无浸润性疾病生存率为80.8%，曲妥珠单抗组为67.1%（差异为13.7个百分点）。T-DM1导致的死亡风险也显著低于曲妥珠单抗（未分层风险比为0.66；95%CI为0.51至0.87；P = 0.003）。T-DM1组7年总生存率为89.1%，曲妥珠单抗组为84.4%（差异为4.7个百分点）。T-DM1组26.1%的患者出现3级或更高等级的不良事件，曲妥珠单抗组为15.7%。
结论
与曲妥珠单抗相比，T-DM1在新辅助治疗后有残余浸润性疾病的HER2阳性早期乳腺癌患者中改善了总生存期，并持续提高了无浸润性疾病生存期。（由F. Hoffmann-La Roche/Genentech资助；KATHERINE临床试验注册号，NCT01772472。）
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