{"title":"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。","authors":"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","doi":"10.1200/JCO.23.02626","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>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 (<i>HER2</i>)-amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing.</p><p><strong>Patients and methods: </strong>Patients exhibited advanced solid tumors with <i>HER2</i> 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.</p><p><strong>Results: </strong>Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated <i>HER2</i> amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma <i>HER2</i> 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 <i>KRAS</i>-mutant colorectal (1/3), <i>PIK3CA</i>-mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma <i>HER2</i> CN above versus below the baseline median value did not differ for impact response; however, clearance of <i>HER2</i> 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.</p><p><strong>Conclusion: </strong>T-DXd treatment demonstrated high ORR with durable response in patients with advanced <i>HER2</i>-amplified solid tumors determined with cfDNA testing.</p>","PeriodicalId":15384,"journal":{"name":"Journal of Clinical Oncology","volume":null,"pages":null},"PeriodicalIF":42.1000,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542975/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1200/JCO.23.02626\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>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 (<i>HER2</i>)-amplified progressive stage solid tumors detected by cell-free DNA (cfDNA) testing.</p><p><strong>Patients and methods: </strong>Patients exhibited advanced solid tumors with <i>HER2</i> 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.</p><p><strong>Results: </strong>Overall, 4,734 patients underwent cfDNA testing from December 2019 to January 2022, and 252 demonstrated <i>HER2</i> amplification. Finally, the study included 62 patients with 16 cancer types with a median baseline plasma <i>HER2</i> 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 <i>KRAS</i>-mutant colorectal (1/3), <i>PIK3CA</i>-mutant endometrial (5/6), and tissue HER2-negative gastric (1/2) cancers. Plasma <i>HER2</i> CN above versus below the baseline median value did not differ for impact response; however, clearance of <i>HER2</i> 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.</p><p><strong>Conclusion: </strong>T-DXd treatment demonstrated high ORR with durable response in patients with advanced <i>HER2</i>-amplified solid tumors determined with cfDNA testing.</p>\",\"PeriodicalId\":15384,\"journal\":{\"name\":\"Journal of Clinical Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":42.1000,\"publicationDate\":\"2024-11-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542975/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1200/JCO.23.02626\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/1 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1200/JCO.23.02626","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/1 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.