转移性乳腺癌内分泌治疗后使用曲妥珠单抗德卢替康

Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer.

作者信息

Bardia Aditya, Hu Xichun, Dent Rebecca, Yonemori Kan, Barrios Carlos H, O'Shaughnessy Joyce A, Wildiers Hans, Pierga Jean-Yves, Zhang Qingyuan, Saura Cristina, Biganzoli Laura, Sohn Joohyuk, Im Seock-Ah, Lévy Christelle, Jacot William, Begbie Natasha, Ke Jun, Patel Gargi, Curigliano Giuseppe

机构信息

From Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, and Massachusetts General Hospital, Boston, MA (A.B.); the Department of Medical Oncology, Fudan University Shanghai Cancer Center, and the Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (X.H.), and Harbin Medical University Cancer Hospital, Harbin (Q.Z.) - all in China; the Division of Medical Oncology, National Cancer Center Singapore, Singapore (R.D.); National Cancer Center Hospital, Tokyo (K.Y.); the Latin American Cooperative Oncology Group, Porto Alegre, Brazil (C.H.B.); Texas Oncology and US Oncology, Baylor University Medical Center, Dallas (J.A.O.); the Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium (H.W.); the Department of Medical Oncology, Institut Curie and Université Paris Cité, Paris (J.-Y.P.), Centre François Baclesse, Caen (C.L.), and the Department of Medical Oncology, Institut du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier (W.J.) - all in France; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (C.S.); the Department of Oncology, Santo Stefano Hospital, Azienda Unità Sanitaria Locale Toscana Centro, Prato (L.B.), and the European Institute of Oncology, IRCCS, and the Department of Oncology and Hematology-Oncology, University of Milan, Milan (G.C.) - all in Italy; the Division of Medical Oncology, Yonsei Cancer Center (J.S.), and the Department of Internal Medicine, Seoul National University Hospital (S.-A.I.) - both in Seoul, South Korea; Clinical Development, Late-Stage Development, Oncology Research and Development, AstraZeneca, Cambridge, United Kingdom (N.B., G.P.); and Biometrics Oncology, Late-Stage Development, Oncology Research and Development, AstraZeneca, Waltham, MA (J.K.).

出版信息

N Engl J Med. 2024 Dec 5;391(22):2110-2122. doi: 10.1056/NEJMoa2407086. Epub 2024 Sep 15.

DOI:10.1056/NEJMoa2407086

PMID:39282896

Abstract

BACKGROUND

Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.

METHODS

We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer. Patients were randomly assigned in a 1:1 ratio to receive trastuzumab deruxtecan or the physician's choice of chemotherapy. The primary end point was progression-free survival (according to blinded independent central review) among the patients with HER2-low disease. Secondary end points included progression-free survival among all the patients who had undergone randomization, overall survival, and safety.

RESULTS

Of the 866 patients who underwent randomization, 713 had HER2-low disease, and 153 had HER2-ultralow disease. Among the patients with HER2-low disease, the median progression-free survival was 13.2 months (95% confidence interval [CI], 11.4 to 15.2) in the trastuzumab deruxtecan group and 8.1 months (95% CI, 7.0 to 9.0) in the chemotherapy group (hazard ratio for disease progression or death, 0.62; 95% CI, 0.52 to 0.75; P<0.001); the results were consistent in the exploratory HER2-ultralow population. Data for overall survival were immature. Adverse events of grade 3 or higher occurred in 52.8% of the patients in the trastuzumab deruxtecan group and in 44.4% of those in the chemotherapy group. Adjudicated interstitial lung disease or pneumonitis occurred in 49 patients (11.3%; three events were grade 5 in severity) and in 1 patient (0.2%; grade 2), respectively.

CONCLUSIONS

Among patients with hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer who had received one or more lines of endocrine-based therapy, treatment with trastuzumab deruxtecan resulted in longer progression-free survival than chemotherapy. No new safety signals were identified. (Funded by AstraZeneca and Daiichi Sankyo; DESTINY-Breast06 ClinicalTrials.gov number, NCT04494425.).

摘要

背景

激素受体阳性转移性乳腺癌患者在接受一线或多线内分泌治疗后，预后会恶化。曲妥珠单抗德鲁昔单抗已显示出对既往接受过化疗、人表皮生长因子受体2（HER2）低表达的转移性乳腺癌患者有效。

方法

我们开展了一项3期、多中心、开放标签试验，纳入激素受体阳性、HER2低表达（免疫组化[IHC]分析评分为1+或2+且原位杂交结果为阴性）或HER2超低表达（IHC 0且有膜染色）的转移性乳腺癌患者，这些患者接受过一线或多线内分泌治疗且未曾接受过转移性乳腺癌的化疗。患者按1:1比例随机分组，分别接受曲妥珠单抗德鲁昔单抗或医生选择的化疗。主要终点是HER2低表达疾病患者的无进展生存期（根据盲态独立中央审查）。次要终点包括所有随机分组患者的无进展生存期、总生存期和安全性。

结果

在866例随机分组的患者中，713例患有HER2低表达疾病，153例患有HER2超低表达疾病。在HER2低表达疾病患者中，曲妥珠单抗德鲁昔单抗组的中位无进展生存期为13.2个月（95%置信区间[CI]，11.4至15.2），化疗组为8.1个月（95%CI，7.0至9.0）（疾病进展或死亡的风险比为0.62；95%CI，0.52至0.75；P<0.001）；在探索性HER2超低表达人群中结果一致。总生存期数据不成熟。曲妥珠单抗德鲁昔单抗组3级或更高等级的不良事件发生在52.8%的患者中，化疗组为44.4%。经判定的间质性肺病或肺炎分别发生在49例患者（11.3%；3例严重程度为5级）和1例患者（0.2%；2级）中。