曲妥珠单抗-德鲁替康与曲妥珠单抗-美坦新用于乳腺癌。
Trastuzumab Deruxtecan versus Trastuzumab Emtansine for Breast Cancer.
机构信息
From the International Breast Cancer Center, Quirónsalud Group, Barcelona, the Scientific Department, Medica Scientia Innovation Research, Valencia, and the Department of Medicine, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Madrid - all in Spain (J. Cortés); Asan Medical Center, University of Ulsan College of Medicine, Ulsan (S.-B.K.), Seoul National University Hospital, Cancer Research Institute (S.-A.I.), and Seoul National University Bundang Hospital (J.H.K.), Seoul National University College of Medicine, and Samsung Medical Center (Y.H.P.), Seoul, and Severance Hospital, Yonsei University, Yonsei (M.H.K.) - all in South Korea; the Department of Oncology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan (W.-P.C.), and the Department of Surgery, Taipei Veterans General Hospital, College of Medicine, National Yang-Ming Chiao Tung University (L.-M.T.), Koo Foundation Sun Yat-Sen Cancer Center (C.-F.C.), and National Taiwan University Hospital and National Taiwan University College of Medicine (C.-S.H.), Taipei - all in Taiwan; Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária (R.H.) and Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (V.P.), São Paulo, and Hospital Nossa Senhora da Conceição, Porto Alegre (J.L.P.) - all in Brazil; Aichi Cancer Center Hospital, Aichi, Japan (H.I.); Sarah Cannon Research Institute, Tennessee Oncology, Nashville (E.H.); the Department of Oncology and Hematology-Oncology, University of Milan, and the Division of Early Drug Development, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico - both in Milan (G.C.); the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (B.X.); the University of Hong Kong, Hong Kong (J.W.Y.C.); Daiichi Sankyo, Basking Ridge, NJ (C.L., Y.L., J. Cathcart, E.B.); AstraZeneca, Gaithersburg, MD (S.V.); and the David Geffen School of Medicine and Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles (S.A.H.).
出版信息
N Engl J Med. 2022 Mar 24;386(12):1143-1154. doi: 10.1056/NEJMoa2115022.
BACKGROUND
Trastuzumab emtansine is the current standard treatment for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer whose disease progresses after treatment with a combination of anti-HER2 antibodies and a taxane.
METHODS
We conducted a phase 3, multicenter, open-label, randomized trial to compare the efficacy and safety of trastuzumab deruxtecan (a HER2 antibody-drug conjugate) with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. The primary end point was progression-free survival (as determined by blinded independent central review); secondary end points included overall survival, objective response, and safety.
RESULTS
Among 524 randomly assigned patients, the percentage of those who were alive without disease progression at 12 months was 75.8% (95% confidence interval [CI], 69.8 to 80.7) with trastuzumab deruxtecan and 34.1% (95% CI, 27.7 to 40.5) with trastuzumab emtansine (hazard ratio for progression or death from any cause, 0.28; 95% CI, 0.22 to 0.37; P<0.001). The percentage of patients who were alive at 12 months was 94.1% (95% CI, 90.3 to 96.4) with trastuzumab deruxtecan and 85.9% (95% CI, 80.9 to 89.7) with trastuzumab emtansine (hazard ratio for death, 0.55; 95% CI, 0.36 to 0.86; prespecified significance boundary not reached). An overall response (a complete or partial response) occurred in 79.7% (95% CI, 74.3 to 84.4) of the patients who received trastuzumab deruxtecan and in 34.2% (95% CI, 28.5 to 40.3) of those who received trastuzumab emtansine. The incidence of drug-related adverse events of any grade was 98.1% with trastuzumab deruxtecan and 86.6% with trastuzumab emtansine, and the incidence of drug-related adverse events of grade 3 or 4 was 45.1% and 39.8%, respectively. Adjudicated drug-related interstitial lung disease or pneumonitis occurred in 10.5% of the patients in the trastuzumab deruxtecan group and in 1.9% of those in the trastuzumab emtansine group; none of these events were of grade 4 or 5.
CONCLUSIONS
Among patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane, the risk of disease progression or death was lower among those who received trastuzumab deruxtecan than among those who received trastuzumab emtansine. Treatment with trastuzumab deruxtecan was associated with interstitial lung disease and pneumonitis. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Breast03 ClinicalTrials.gov number, NCT03529110.).
背景
曲妥珠单抗-美坦新偶联物（trastuzumab emtansine）是目前治疗人表皮生长因子受体 2（HER2）阳性转移性乳腺癌的标准治疗方法，此类患者在接受抗 HER2 抗体和紫杉烷类药物联合治疗后疾病进展。
方法
我们开展了一项 3 期、多中心、开放标签、随机试验，旨在比较曲妥珠单抗-美坦新偶联物（trastuzumab deruxtecan）与曲妥珠单抗 emtansine 治疗先前接受曲妥珠单抗和紫杉烷类药物治疗的 HER2 阳性转移性乳腺癌患者的疗效和安全性。主要终点是无进展生存期（由盲法独立中心评估确定）；次要终点包括总生存期、客观缓解率和安全性。
结果
在 524 例随机分配的患者中，接受曲妥珠单抗-美坦新偶联物治疗的患者在 12 个月时无疾病进展的生存率为 75.8%（95%置信区间 [CI]，69.8 至 80.7），而接受曲妥珠单抗 emtansine 治疗的患者为 34.1%（95% CI，27.7 至 40.5）（任何原因导致的进展或死亡的风险比 [HR]，0.28；95% CI，0.22 至 0.37；P<0.001）。接受曲妥珠单抗-美坦新偶联物治疗的患者在 12 个月时的生存率为 94.1%（95% CI，90.3 至 96.4），而接受曲妥珠单抗 emtansine 治疗的患者为 85.9%（95% CI，80.9 至 89.7）（死亡风险比，0.55；95% CI，0.36 至 0.86；预设意义边界未达到）。接受曲妥珠单抗-美坦新偶联物治疗的患者中有 79.7%（95% CI，74.3 至 84.4）发生了总体缓解（完全或部分缓解），而接受曲妥珠单抗 emtansine 治疗的患者中为 34.2%（95% CI，28.5 至 40.3）。任何等级的药物相关不良事件发生率为曲妥珠单抗-美坦新偶联物组 98.1%，曲妥珠单抗 emtansine 组 86.6%，药物相关 3 级或 4 级不良事件发生率分别为曲妥珠单抗-美坦新偶联物组 45.1%和曲妥珠单抗 emtansine 组 39.8%。曲妥珠单抗-美坦新偶联物组 10.5%的患者发生药物相关间质性肺病或肺炎，而曲妥珠单抗 emtansine 组为 1.9%；这些事件均无 4 级或 5 级。
结论
在先前接受曲妥珠单抗和紫杉烷类药物治疗的 HER2 阳性转移性乳腺癌患者中，与接受曲妥珠单抗 emtansine 治疗的患者相比，接受曲妥珠单抗-美坦新偶联物治疗的患者疾病进展或死亡的风险更低。曲妥珠单抗-美坦新偶联物治疗与间质性肺病和肺炎有关。（由 Daiichi Sankyo 和 AstraZeneca 资助；DESTINY-Breast03 ClinicalTrials.gov 编号，NCT03529110。）
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