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A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer

Authors
 Choong-Kun Lee  ;  Sun Young Rha  ;  Hyo Song Kim  ;  Minkyu Jung  ;  Beodeul Kang  ;  Jingmin Che  ;  Woo Sun Kwon  ;  Sejung Park  ;  Woo Kyun Bae  ;  Dong-Hoe Koo  ;  Su-Jin Shin  ;  Hyunki Kim  ;  Hei-Cheul Jeung  ;  Dae Young Zang  ;  Sang Kil Lee  ;  Chung Mo Nam  ;  Hyun Cheol Chung 
Citation
 NATURE COMMUNICATIONS, Vol.13(1) : 6002, 2022-10 
Journal Title
NATURE COMMUNICATIONS
Issue Date
2022-10
MeSH
Antibodies, Monoclonal, Humanized / therapeutic use ; Antineoplastic Combined Chemotherapy Protocols* / adverse effects ; Humans ; Receptor, ErbB-2 / genetics ; Receptor, ErbB-2 / metabolism ; Stomach Neoplasms* / drug therapy ; Stomach Neoplasms* / genetics ; Trastuzumab / therapeutic use
Abstract
In this multi-center phase II trial, we evaluated the efficacy and safety of a quadruplet regimen (pembrolizumab, trastuzumab, and doublet chemotherapy) as first-line therapy for unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) (NCT02901301). The primary endpoints were recommended phase 2 dose (RP2D) for phase Ib and objective response rate (ORR) for phase II. The secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, time to response and safety. Without dose-limiting or unexpected toxicities, the starting dose in the phase Ib trial was selected as RP2D. In 43 patients, the primary endpoint was achieved: the objective response rate was 76.7% (95% confidence interval [CI]: 61.4-88.2), with complete and partial responses in 14% and 62.8% of patients, respectively. The median progression-free survival, overall survival, and duration of response were 8.6 months, 19.3 months, and 10.8 months, respectively. No patients discontinued pembrolizumab because of immune-related adverse events. Programmed death ligand-1 status was not related to survival. Post hoc analyses of pretreatment tumor specimens via targeted sequencing indicated that ERBB2 amplification, RTK/RAS pathway alterations, and high neoantigen load corrected by HLA-B were positively related to survival. The current quadruplet regimen shows durable efficacy and safety for patients with HER2-positive AGC.
Files in This Item:
T202204899.pdf Download
DOI
10.1038/s41467-022-33267-z
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Preventive Medicine (예방의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyunki(김현기) ORCID logo https://orcid.org/0000-0003-2292-5584
Kim, Hyo Song(김효송) ORCID logo https://orcid.org/0000-0002-0625-9828
Nam, Chung Mo(남정모) ORCID logo https://orcid.org/0000-0003-0985-0928
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Shin, Su Jin(신수진) ORCID logo https://orcid.org/0000-0001-9114-8438
Lee, Sang Kil(이상길) ORCID logo https://orcid.org/0000-0002-0721-0364
Lee, Choong-kun(이충근) ORCID logo https://orcid.org/0000-0001-5151-5096
Jung, Min Kyu(정민규) ORCID logo https://orcid.org/0000-0001-8281-3387
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/192246
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