SCI

27 August 2024

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

（J Clin Oncol;IF:42.1）

  • Yagisawa M, Taniguchi H, Satoh T, Kadowaki S, Sunakawa Y, Nishina T, Komatsu Y, Esaki T, Sakai D, Doi A et al: 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. J Clin Oncol 2024:Jco2302626.

  • Correspondence to：Hiroya Taniguchi, MD, PhD; e-mail: hiroya.taniguchi@aichi-cc.jp.

PURPOSE 目的

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.

HERALD/EPOC1806是一项多中心2期试验，在游离DNA (cfDNA)检测出人表皮生长因子受体2 (HER2)扩增的进展期实体瘤患者中评估了曲妥珠单抗- Deruxtecan (T-DXd)疗法

 

PATIENTS AND METHODS 患者与方法

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.

患者表现为晚期实体瘤，通过cfDNA检测的，二代测序确定HER2扩增，不需要进行免疫组化HER2检测。试验组每3周给予T-DXd 5.4 mg/kg，直至出现疾病进展或不可耐受的不良反应。

 

RESULTS 结果

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.

总体而言，从2019年12月至2022年1月，4,734例患者接受了cfDNA检测，252例证实了HER2扩增。最终，该研究纳入了62例患者，包括16种癌症类型，中位基线血浆HER2拷贝数(CN)为8.55(范围，2.4 ~ 73.9)。总缓解率(ORR)为56.5% (95% CI, 43.3 ~ 69.0)，该值超过了5%的阈值。本试验评估了13种癌症类型的疗效，包括kras突变型结直肠癌(1/3)、PIK3CA突变型子宫内膜癌(5/6)和组织HER2阴性胃癌(1/2)。血浆HER2 CN高于或低于基线中位数对疗效的影响无差异; 然而，与持续治疗相比，在第2周期第1天清除cfDNA中的HER2扩增具有更高的缓解值。中位无进展生存期和反应持续时间分别为7.0个月(95% CI, 4.9 ~ 9.7)和8.8个月(95% CI, 5.8 ~ 11.2)，大多数并发症为轻至中度。16例(26%)患者发生了间质性肺疾病，其中1级14例，2级1例，3级1例。

 

CONCLUSION 结论

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

在通过cfDNA检测确定的晚期HER2扩增的实体瘤患者中，T-DXd治疗显示出高ORR和持久缓解。