Patient-reported outcomes with trastuzumab deruxtecan in hormone receptor-positive, HER2-low or HER2-ultralow metastatic breast cancer: results from the randomized DESTINY-Breast06 trial

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-05-01 DOI:10.1016/j.esmoop.2025.105082

X. Hu , G. Curigliano , K. Yonemori , A. Bardia , C.H. Barrios , J. Sohn , C. Lévy , W. Jacot , J. Tsurutani , A. Roborel de Climens , X. Wu , A. Andrzejuk-Ćwik , Z. Mbanya , R. Dent

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引用次数: 0

Abstract

Background

The randomized phase III DESTINY-Breast06 trial (NCT04494425) demonstrated superior efficacy with trastuzumab deruxtecan (T-DXd) versus chemotherapy treatment of physician’s choice (TPC) and no new safety signals in patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-low [immunohistochemistry (IHC) 1+, IHC 2+/in situ hybridization-negative], and HER2-ultralow (IHC 0 with membrane staining) metastatic breast cancer (mBC). Here, we report the patient-reported outcome (PRO) endpoints in the intent-to-treat (ITT; HER2-low/-ultralow) and HER2-low populations.

Patients and methods

Patients with progressive disease (PD) after one or more prior lines of endocrine-based therapy and no prior chemotherapy for mBC were assigned 1 : 1 to T-DXd 5.4 mg/kg once every 3 weeks (n = 436) or TPC [n = 430; 59.8% capecitabine; 24.4% nab-paclitaxel; and 15.8% paclitaxel]. PRO questionnaires included the European Organisation for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire (QLQ-C30) and breast cancer-specific module (EORTC QLQ-BR45). Changes from baseline (CFB; earliest of 31 weeks or on-study PD) and time to deterioration were assessed.

Results

The median treatment duration was 11.0 (T-DXd) versus 5.6 (TPC) months. In the ITT, the mean CFB scores were similar across treatments in EORTC QLQ-C30 global health status/quality of life (QOL) and functioning scales. T-DXd was associated with less pain [adjusted mean difference −7.2, 95% confidence interval (CI) −9.9 to −4.5] and fewer skin/mucosal symptoms (adjusted mean difference −9.5, 95% CI −11.5 to −7.5), but more nausea/vomiting (adjusted mean difference 7.2, 95% CI 5.3-9.2), appetite loss (adjusted mean difference 6.8, 95% CI 3.6-10.0), and constipation (adjusted mean difference 5.5, 95% CI 2.6-8.4) versus TPC. T-DXd reduced the risk of clinically meaningful deterioration in physical/role/emotional functioning, pain, and fatigue versus TPC, but increased the risk of deterioration in gastrointestinal symptoms. Results were similar in the HER2-low population.

Conclusions

T-DXd preserved QOL while delaying deterioration in physical/role/emotional functioning, pain, and fatigue versus TPC, albeit with more gastrointestinal symptoms. PRO data complement the efficacy/safety of T-DXd in this population.

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患者报告的曲妥珠单抗治疗激素受体阳性、her2低或her2超低转移性乳腺癌的结果：来自DESTINY-Breast06随机试验的结果

随机III期试验（NCT04494425）表明，曲妥珠单抗德鲁西替康（T-DXd）与医生选择的化疗（TPC）相比，在激素受体阳性、人表皮生长因子受体2 （HER2）低[免疫组织化学（IHC） 1+、IHC 2+/原位杂交阴性]和HER2-超低（膜染色IHC 0）转移性乳腺癌（mBC）患者中没有新的安全性信号。在这里，我们报告了患者报告的治疗意向（ITT）终点（PRO）；her2低/-超低)和her2低人群。患者和方法：既往接受过一种或多种内分泌治疗且无化疗史的进行性疾病（PD）患者，每3周1次（n = 436）， 1比1接受T-DXd （5.4 mg/kg）或TPC (n = 430；卡培他滨59.8%;nab-paclitaxel 24.4%;15.8%紫杉醇]。PRO问卷包括欧洲癌症研究与治疗组织（EORTC）核心生活质量问卷（QLQ-C30）和乳腺癌特异性模块（EORTC QLQ-BR45）。基线变化(CFB；最早31周或研究中PD)和恶化时间。结果中位治疗时间分别为11.0 （T-DXd）和5.6 （TPC）个月。在ITT中，在EORTC QLQ-C30全球健康状态/生活质量（QOL）和功能量表上，不同治疗的平均CFB评分相似。与TPC相比，T-DXd与更少的疼痛（校正平均差值- 7.2,95%可信区间(CI) - 9.9至- 4.5）和更少的皮肤/粘膜症状（校正平均差值- 9.5,95% CI - 11.5至- 7.5）相关，但更多的恶心/呕吐（校正平均差值- 7.2,95% CI - 5.3-9.2）、食欲下降（校正平均差值- 6.8,95% CI 3.6-10.0）和便秘（校正平均差值- 5.5,95% CI 2.6-8.4）相关。与TPC相比，T-DXd降低了临床意义上的身体/角色/情绪功能、疼痛和疲劳恶化的风险，但增加了胃肠道症状恶化的风险。her2低人群的结果相似。结论与TPC相比，st - dxd保留了患者的生活质量，延缓了身体/角色/情绪功能、疼痛和疲劳的恶化，尽管有更多的胃肠道症状。PRO数据补充了T-DXd在该人群中的有效性/安全性。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.