曲妥珠单抗地屈孕酮治疗通过血浆游离 DNA 检测发现人表皮生长因子受体 2 扩增的晚期实体瘤:多中心、单臂、II 期篮式试验。

IF 42.1 1区 医学 Q1 ONCOLOGY
Journal of Clinical Oncology Pub Date : 2024-11-10 Epub Date: 2024-08-01 DOI:10.1200/JCO.23.02626
Masataka Yagisawa, Hiroya Taniguchi, Taroh Satoh, Shigenori Kadowaki, Yu Sunakawa, Tomohiro Nishina, Yoshito Komatsu, Taito Esaki, Daisuke Sakai, Ayako Doi, Takeshi Kajiwara, Hiromi Ono, Masatoshi Asano, Nami Hirano, Justin Odegaard, Satoshi Fujii, Shogo Nomura, Hideaki Bando, Akihiro Sato, Takayuki Yoshino, Yoshiaki Nakamura
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引用次数: 0

摘要

目的:HERALD/EPOC1806是一项多中心II期试验,评估通过无细胞DNA(cfDNA)检测发现的人表皮生长因子受体2(HER2)扩增进展期实体瘤患者的曲妥珠单抗德鲁司坦(T-DXd)疗法:患者均为晚期实体瘤患者,其HER2扩增是通过cfDNA检测的新一代测序确定的,无需进行免疫组化HER2检测。研究组接受T-DXd治疗,剂量为5.4 mg/kg,每3周一次,直至疾病进展或出现不可耐受的毒性:从2019年12月到2022年1月,共有4734名患者接受了cfDNA检测,其中252名患者的HER2扩增。最后,该研究共纳入了62名患者,16种癌症类型,血浆HER2拷贝数(CN)中位数为8.55(范围为2.4-73.9)。根据研究者的评估,确认的总体反应率(ORR)为 56.5%(95% CI,43.3 至 69.0),从而显示出超过 5%阈值的数值。对 13 种癌症类型的反应进行了评估,包括 KRAS 突变的结直肠癌(1/3)、PIK3CA 突变的子宫内膜癌(5/6)和组织 HER2 阴性的胃癌(1/2)。血浆 HER2 CN 高于和低于基线中位值对反应的影响没有差异;但是,在第 2 周期第 1 天清除 cfDNA 中的 HER2 扩增与持续存在相比,反应值更高。中位无进展生存期和应答持续时间分别为7.0(95% CI,4.9至9.7)个月和8.8(95% CI,5.8至11.2)个月,大多数并发症为轻度至中度。16例(26%)患者出现肺间质疾病,其中14例为1级疾病,1例为2级疾病,1例为3级疾病:结论:T-DXd治疗对通过cfDNA检测确定的晚期HER2扩增实体瘤患者具有高ORR和持久应答。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Trastuzumab Deruxtecan in Advanced Solid Tumors With Human Epidermal Growth Factor Receptor 2 Amplification Identified by Plasma Cell-Free DNA Testing: A Multicenter, Single-Arm, Phase II Basket Trial.

Purpose: HERALD/EPOC1806 was conducted as a multicenter phase II trial assessing trastuzumab deruxtecan (T-DXd) therapy for patients with human epidermal growth factor receptor 2 (HER2)-amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing.

Patients and methods: Patients exhibited advanced solid tumors with HER2 amplification that was identified via next-generation sequencing of cfDNA testing, without the requirement for immunohistochemical HER2 testing. The studied group was administered T-DXd at 5.4 mg/kg once every 3 weeks until onset of disease progression or intolerable toxicity.

Results: Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated HER2 amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma HER2 copy number (CN) of 8.55 (range, 2.4-73.9). Confirmed overall response rate (ORR) by investigator assessment was 56.5% (95% CI, 43.3 to 69.0), thus showing a value beyond the 5% threshold. Responses were evaluated for 13 cancer types, including KRAS-mutant colorectal (1/3), PIK3CA-mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma HER2 CN above versus below the baseline median value did not differ for impact response; however, clearance of HER2 amplification in cfDNA on cycle 2 day 1 had higher response values compared with persistence. Median progression-free survival and response duration were 7.0 (95% CI, 4.9 to 9.7) and 8.8 (95% CI, 5.8 to 11.2) months, respectively, with the majority of complications being mild to moderate. Interstitial lung diseases were identified in 16 (26%) patients, including 14 patients with grade 1 disease, one patient with grade 2 disease, and one patient with grade 3 disease.

Conclusion: T-DXd treatment demonstrated high ORR with durable response in patients with advanced HER2-amplified solid tumors determined with cfDNA testing.

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来源期刊
Journal of Clinical Oncology
Journal of Clinical Oncology 医学-肿瘤学
CiteScore
41.20
自引率
2.20%
发文量
8215
审稿时长
2 months
期刊介绍: The Journal of Clinical Oncology serves its readers as the single most credible, authoritative resource for disseminating significant clinical oncology research. In print and in electronic format, JCO strives to publish the highest quality articles dedicated to clinical research. Original Reports remain the focus of JCO, but this scientific communication is enhanced by appropriately selected Editorials, Commentaries, Reviews, and other work that relate to the care of patients with cancer.
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