根据入组 HER2 IHC 状态确定曲妥珠单抗德鲁司坦对 HER2 表达实体瘤的疗效：DESTINY-PanTumor02的事后分析

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL Advances in Therapy Pub Date : 2024-09-11 DOI:10.1007/s12325-024-02975-x

Ana Oaknin, Jung-Yun Lee, Vicky Makker, Do-Youn Oh, Susana Banerjee, Antonio González-Martín, Kyung Hae Jung, Iwona Ługowska, Luis Manso, Aránzazu Manzano, Bohuslav Melichar, Salvatore Siena, Daniil Stroyakovskiy, Anitra Fielding, Soham Puvvada, Ann Smith, Funda Meric-Bernstam

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引用次数: 0

摘要

导读：DESTINY-PanTumor02（NCT04482309）评估了曲妥珠单抗德鲁司坦（T-DXd）在人表皮生长因子受体2（HER2）表达[免疫组化（IHC）3+/2+]实体瘤预处理患者中的疗效和安全性，涉及七个组群：子宫内膜、宫颈、卵巢、膀胱、胆道、胰腺和其他。按 HER2 状态进行的亚组分析之前已通过中心 HER2 IHC 检测进行了报告，这些检测结果在入组时确定或通过回顾性分析确认。为了反映临床实践中可用的检测方法，大多数患者（n = 202；75.7%）是根据局部 HER2 IHC 检测入组的。方法这项2期开放标签研究评估了T-DXd（5.4 mg/kg，每3周1次）用于治疗HER2表达（经局部或中心检测为IHC 3+/2+）的局部晚期或转移性疾病，这些患者均接受过≥1次系统治疗或未接受替代治疗。主要终点是研究者评估确认的客观反应率（ORR）。次要终点包括安全性、反应持续时间（DOR）、无进展生存期（PFS）和总生存期。结果分别有111例（41.6%）和151例（56.6%）IHC 3+和IHC 2+肿瘤患者入组。在IHC 3+肿瘤患者中，研究者评估确认的ORR为51.4%[95%置信区间（CI）41.7, 61.0]，中位DOR为14.2个月（95% CI 10.3, 23.6）。在 IHC 2+ 肿瘤患者中，研究者评估的 ORR 为 26.5%（95% CI 19.6，34.3），中位 DOR 为 9.8 个月（95% CI 4.5，12.6）。结论与之前报道的结果一致，T-DXd在HER2表达肿瘤患者中显示出有临床意义的获益，其中IHC 3+肿瘤患者获益最大。这些数据支持T-DXd在HER2表达实体瘤中的抗肿瘤活性，无论患者是通过局部还是中央HER2 IHC检测确定的。

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Efficacy of Trastuzumab Deruxtecan in HER2-Expressing Solid Tumors by Enrollment HER2 IHC Status: Post Hoc Analysis of DESTINY-PanTumor02

Introduction

DESTINY-PanTumor02 (NCT04482309) evaluated the efficacy and safety of trastuzumab deruxtecan (T-DXd) in pretreated patients with human epidermal growth factor receptor 2 (HER2)-expressing [immunohistochemistry (IHC) 3+/2+] solid tumors across seven cohorts: endometrial, cervical, ovarian, bladder, biliary tract, pancreatic, and other. Subgroup analyses by HER2 status were previously reported by central HER2 IHC testing, determined at enrollment or confirmed retrospectively. Reflecting the testing methods available in clinical practice, most patients (n = 202; 75.7%) were enrolled based on local HER2 IHC testing. Here, we report outcomes by HER2 IHC status as determined by the local or central test results used for study enrollment.

Methods

This phase 2, open-label study evaluated T-DXd (5.4 mg/kg once every 3 weeks) for HER2-expressing (IHC 3+/2+ by local or central testing) locally advanced or metastatic disease after ≥ 1 systemic treatment or without alternative treatments. The primary endpoint was investigator-assessed confirmed objective response rate (ORR). Secondary endpoints included safety, duration of response (DOR), progression-free survival (PFS), and overall survival.

Results

In total, 111 (41.6%) and 151 (56.6%) patients were enrolled with IHC 3+ and IHC 2+ tumors, respectively. In patients with IHC 3+ tumors, investigator-assessed confirmed ORR was 51.4% [95% confidence interval (CI) 41.7, 61.0], and median DOR was 14.2 months (95% CI 10.3, 23.6). In patients with IHC 2+ tumors, investigator-assessed ORR was 26.5% (95% CI 19.6, 34.3), and median DOR was 9.8 months (95% CI 4.5, 12.6). Safety was consistent with the known profile of T-DXd.

Conclusion

In line with previously reported results, T-DXd demonstrated clinically meaningful benefit in patients with HER2-expressing tumors, with the greatest benefit in patients with IHC 3+ tumors. These data support the antitumor activity of T-DXd in HER2-expressing solid tumors, irrespective of whether patients are identified by local or central HER2 IHC testing.

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.