乳腺癌命运交响曲（DESTINY-Breast）系列研究已经证实，德曲妥珠单抗对HER2阳性晚期乳腺癌的疗效显著提高，虽然这些研究都入组了脑转移患者，但是各自样本量太小，故有必要对这些研究HER2阳性晚期乳腺癌脑转移患者的疗效进行汇总分析。 2024年9月4日，欧洲肿瘤内科学会官方期刊《肿瘤学年鉴》在线发表法国古斯塔夫鲁西癌症中心、西班牙巴塞罗那国际乳腺癌中心、巴塞罗那医学创新研究中心、马德里欧罗巴大学、马德里肿瘤医院、玛丽亚安娜慈善医院、意大利米兰大学欧洲肿瘤研究院、美国第一三共、纽约纪念医院斯隆凯特林癌症中心、耶鲁大学癌症中心、华盛顿大学弗雷德哈钦森癌症中心、中国吉林大学第一医院、台南成功大学医院、台北荣民总医院、韩国成均馆大学医学院三星首尔医院、蔚山大学医学院首尔峨山医院、首尔国立大学医院、日本第一三共、神奈川癌症中心、东京株式会社、巴西康塞桑圣母医院、德国慕尼黑综合癌症中心、慕尼黑大学医院的探索性研究报告，汇总分析了德曲妥珠单抗对HER2阳性晚期乳腺癌基线时已有脑转移患者的有效性和安全性，并且根据既往局部治疗进行了分类。 该汇总分析的德曲妥珠单抗数据来自乳腺癌命运交响曲一号、二号和三号研究，对照数据来自接受医生选择治疗方案或者恩美曲妥珠单抗的患者，分别来自乳腺癌命运交响曲二号和三号研究。根据美国食品药品监督管理局标准评定基线时已有脑转移状态。终点包括根据实体肿瘤疗效评价标准1.1版进行盲法独立集中审核的颅内客观缓解（脑内完全或部分缓解）、颅内缓解时间、颅内缓解持续时间、盲法独立集中审核的中枢神经系统无进展生存、总生存和安全性。 结果，148例接受德曲妥珠单抗治疗患者和83例接受对照治疗患者基线时已有脑转移。 对于德曲妥珠单抗治疗患者，既往已治疗/稳定型与既往未治疗/活动型脑转移患者相比：- 颅内缓解中位时间：2.8个月比1.5个月（范围：1.1～13.9、1.2～13.7个月）
- 颅内缓解中位持续：12.3个月比17.5个月（95%置信区间：9.1～17.9、13.6～31.6个月）
- 中枢神经系统中位无进展生存：12.3个月比18.5个月（95%置信区间：11.1～13.8、13.6～23.3个月）
- 中位总生存：未达中位比30.2个月（95%置信区间：22.1个月～无法估计、21.3个月～无法估计）
对于德曲妥珠单抗治疗患者，有脑转移与无脑转移相比，≥3级药物相关治疗期间不良事件发生率为43.2%比46.4%。 因此，该汇总分析结果表明，对于HER2阳性晚期乳腺癌脑转移患者，无论既往已治疗或稳定型，还是既往未治疗或活动型，德曲妥珠单抗都表现出有显著临床意义的颅内疗效和临床获益，安全性可接受且易于管理。Ann Oncol. 2024 Sep 4. IF: 56.7A Pooled Analysis of Trastuzumab Deruxtecan in Patients With HER2-Positive Metastatic Breast Cancer With Brain Metastases.André F, Cortés J, Curigliano G, Modi S, Li W, Park YH, Chung WP, Kim SB, Yamashita T, Pedrini JL, Im SA, Tseng LM, Harbeck N, Krop I, Nakatani S, Tecson K, Ashfaque S, Egorov A, Hurvitz SA.Gustave Roussy, Villejuif, France; International Breast Cancer Center, Pangaea Oncology, Quiron Group, Barcelona, Spain; Medica Scientia Innovation Research, Barcelona, Spain, and Ridgewood, New Jersey; Universidad Europea de Madrid, Madrid, Spain; IOB Madrid, Hospital Beata Maria Ana, Madrid, Spain; University of Milan, Milan, Italy; European Institute of Oncology, IRCCS, Milan, Italy; Memorial Sloan Kettering Cancer Center, New York, NY, USA; The First Hospital of Jilin University, Changchun, China; Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Asan Medical Center, Seoul, Republic of Korea; Kanagawa Cancer Center, Yokohama, Japan; Hospital Nossa Senhora da Conceicao, Porto Alegre, Brazil; Seoul National University Hospital, Seoul, Republic of Korea; Taipei Veterans General Hospital, Taipei, Taiwan; Comprehensive Cancer Center Munich, LMU University Hospital, Munich, Germany; Yale Cancer Center, New Haven, CT, USA; Daiichi Sankyo Co., Ltd., Tokyo, Japan; Daiichi Sankyo Inc., Basking Ridge, NJ, USA; University of Washington and Fred Hutchinson Cancer Center, Seattle, WA, USA.- T-DXd data were pooled from DESTINY-Breast01/-02/-03
- Intracranial ORR with T-DXd was 45.2% and 45.5% in patients with treated/stable and untreated/active BMs, respectively
- Median CNS-PFS with T-DXd was 12.3 and 18.5 months in patients with treated/stable and untreated/active BMs, respectively
- Median OS with T-DXd was not reached and 30.2 months in patients with treated/stable and untreated/active BMs, respectively
- T-DXd showed meaningful intracranial efficacy in patients with HER2-positive mBC with treated/stable and active BMs
BACKGROUND: This exploratory pooled analysis investigated the efficacy and safety of trastuzumab deruxtecan (T-DXd) versus comparator treatment in patients with HER2-positive metastatic breast cancer (mBC) with brain metastases (BMs) at baseline, categorized according to previous local treatment.PATIENTS AND METHODS: T-DXd data were pooled from DESTINY-Breast01/-02/-03. Comparator data, from patients receiving physician's choice therapy and trastuzumab emtansine, were pooled from DESTINY-Breast02 and -03, respectively. Baseline BM status was assessed according to US Food and Drug Administration criteria. Endpoints included intracranial objective response rate (ORR; complete or partial response in brain) per blinded independent central review (BICR) by RECIST v1.1, time to intracranial response, intracranial duration of response (DoR), central nervous system progression-free survival (CNS-PFS) by BICR, overall survival (OS), and safety.RESULTS: 148 patients who received T-DXd and 83 patients who received comparator treatment had BMs at baseline. In those who were treated with T-DXd, the intracranial ORR of patients with treated/stable and untreated/active BMs was 45.2% and 45.5%, respectively. The median (range) time to intracranial response was 2.8 months (1.1-13.9 months) and 1.5 months (1.2-13.7 months) in patients with treated/stable and untreated/active BMs, respectively. For those with treated/stable BMs, the median (95% CI) intracranial DoR was 12.3 months (9.1-17.9 months), and for those with untreated/active BMs it was 17.5 months (13.6-31.6 months). The median (95% CI) CNS-PFS and OS was 12.3 months (11.1-13.8 months) and not reached (22.1 months-not estimable [NE]) in those with treated/stable BMs, and 18.5 months (13.6-23.3 months) and 30.2 months (21.3 months-NE) in those with untreated/active BMs, respectively. Drug-related TEAEs grade ≥3 were experienced by 43.2% of patients with BMs and 46.4% without BMs with T-DXd.CONCLUSIONS: T-DXd demonstrated meaningful intracranial efficacy and clinical benefit in OS, with an acceptable and manageable safety profile in patients with HER2-positive mBC with treated/stable and untreated/active BMs.KEYWORDS: metastatic breast cancer, HER2+, brain metastases, trastuzumab deruxtecan, pooled analysis, intracranialDOI: 10.1016/j.annonc.2024.08.2347
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