新英格兰：死亡风险降低三分之一
学术
健康
2025-01-16 15:18
上海
对于HER2阳性早期乳腺癌患者，术前化疗联合HER2靶向治疗后，45%至66%的病例在手术时仍然残留浸润癌，与病理完全缓解患者相比，复发或死亡风险高2.86倍。2018年12月5日，全球规模最大的乳腺癌学术会议第41届圣安东尼奥乳腺癌研讨会和国际四大医学期刊之一《新英格兰医学杂志》同时公布KATHERINE研究中期分析结果，首次证实恩美曲妥珠单抗可将HER2阳性早期乳腺癌术前治疗后仍然残留浸润癌患者术后3年复发或死亡风险降低50%，从而被写入指南。如今已过6年，恩美曲妥珠单抗对这些患者术后复发或死亡风险的长期影响如何？- KATHERINE (NCT01772472): A Study of Trastuzumab Emtansine (Kadcyla) Versus Trastuzumab as Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Who Have Residual Tumor in the Breast or Axillary Lymph Nodes Following Preoperative Therapy
- Official Title: A Randomized, Multicenter, Open-Label Phase III Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine Versus Trastuzumab as Adjuvant Therapy for Patients With HER2-Positive Primary Breast Cancer Who Have Residual Tumor Present Pathologically in the Breast or Axillary Lymph Nodes Following Preoperative Therapy
2025年1月16日，国际四大医学期刊之一、创刊213周年的美国麻省医学会官方期刊《新英格兰医学杂志》在线发表全国乳腺癌大肠癌术后辅助治疗研究协作组（NSABP）首席科学官兼乳腺癌委员会主席、匹兹堡大学医学院希尔曼癌症中心查尔斯·盖耶教授等全球34位知名学者（其中包括复旦大学附属肿瘤医院邵志敏教授）代表KATHERINE研究协作组撰写的预设无浸润癌生存最终分析和总生存第二次中期分析。 该国际多中心非盲随机对照三期临床研究于2013年4月～2015年12月从28个国家地区273家医疗机构入组HER2阳性早期乳腺癌术前曲妥珠单抗＋紫杉类±蒽环类化疗后发现乳房或腋窝残留浸润癌患者1486例，按1比1随机分为两组，每3周给予恩美曲妥珠单抗（743例）或曲妥珠单抗（743例）连续14个周期。 结果，中位随访8.4年时，恩美曲妥珠单抗与曲妥珠单抗相比：- 浸润癌或死亡风险：降低46%（未分层风险比：0.54，95%置信区间：0.44～0.66）
- 7年无浸润癌生存率：高13.7个百分点（80.8%比67.1%）
- 死亡风险：降低34%（未分层风险比：0.66，95%置信区间：0.51～0.87，P=0.003）
- 7年总生存率：提高4.7个百分点（89.1%比84.4%）
恩美曲妥珠单抗与曲妥珠单抗相比，≥3级不良事件发生率分别为26.1%比15.7%。 因此，该研究长期随访结果表明，对于HER2阳性早期乳腺癌术前治疗后残留浸润癌患者，恩美曲妥珠单抗与曲妥珠单抗相比，死亡风险降低三分之一，总生存率显著提高，并可持续降低浸润癌或死亡风险将近一半、显著提高无浸润癌生存率。 对此，第一作者查尔斯·盖耶教授表示：作为肿瘤科医师，我们很贪心，除非我们的乳腺癌患者无癌生存达到100%，否则我们永远不会满足。N Engl J Med. 2025 Jan 16;392(3):249-257. IF: 96.2Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.Geyer CE Jr, Untch M, Huang CS, Mano MS, Mamounas EP, Wolmark N, Rastogi P, Schneeweiss A, Redondo A, Fischer HH, D'Hondt V, Conlin AK, Guarneri V, Wapnir IL, Jackisch C, Arce-Salinas C, Fasching PA, DiGiovanna MP, Crown JP, Wuelfing P, Shao Z, Rota Caremoli E, Bonnefoi HR, Hennessy BT, Stamatovic L, Castro-Salguero H, Brufsky AM, Knott A, Siddiqui A, Lambertini C, Boulet T, Nyawira B, Restuccia E, Loibl S; KATHERINE Study Group.National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation, University of Pittsburgh School of Medicine-UPMC Hillman Cancer Center, Pittsburgh; AGO-B and Helios Klinikum Berlin-Buch, Berlin; National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg; Evangelische Kliniken Gelsenkirchen, Gelsenkirchen;, Arbeitsgemeinschaft Gynakologische Onkologie-Breast and Sana Klinikum Offenbach, Offenbach; University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen; German Breast Group, Neu-Isenburg; Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt, Germany; National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Instituto do Cancer do Estado de Sao Paulo, Sao Paulo; Orlando Health Cancer Institute, Orlando, FL; Hospital Universitario La Paz-Instituto de Investigación del Hospital Universitario La Paz, Madrid; L'Institut du Cancer de Montpellier-Val d'Aurelle, Montpellier; Institut Bergonié, INSERM Unité 1312, and Université de Bordeaux UFR Sciences Médicales, Bordeaux, France; Providence Cancer Institute, Portland, OR; the Department of Surgery, Oncology, and Gastroenterology, University of Padua, and Oncology 2, Istituto Oncologico Veneto IRCCS, Padua; Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy; Stanford University School of Medicine, Stanford, CA; National Cancer Institute, Mexico City; Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT; All-Ireland Cooperative Oncology Research Group, Beaumont RCSI Cancer Centre, Cancer Trials Ireland, Dublin; Fudan University Shanghai Cancer Center, Shanghai, China; Institute for Oncology and Radiology of Serbia, Belgrade; Grupo Médico Angeles, Guatemala City, Guatemala; Roche Products, Welwyn Garden City, United Kingdom; F. Hoffmann-La Roche, Basel, Switzerland.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/GenentechKATHERINE ClinicalTrials.gov number, NCT01772472DOI: 10.1056/NEJMoa2406070
