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Open-Label, Multicenter, Randomized, Biomarker-Integrated Umbrella Trial for Second-Line Treatment of Advanced Gastric Cancer: K-Umbrella Gastric Cancer Study

Authors
 Choong-Kun Lee  ;  Hyo Song Kim  ;  Minkyu Jung  ;  Hyunki Kim  ;  Woo Kyun Bae  ;  Dong-Hoe Koo  ;  Hei Cheul Jeung  ;  Sook Ryun Park  ;  In Gyu Hwang  ;  Dae Young Zang  ;  Hyun Woo Lee  ;  Sejung Park  ;  Chung Mo Nam  ;  Hyun Cheol Chung  ;  Sun Young Rha 
Citation
 JOURNAL OF CLINICAL ONCOLOGY, Vol.42(3) : 348-357, 2024-01 
Journal Title
JOURNAL OF CLINICAL ONCOLOGY
ISSN
 0732-183X 
Issue Date
2024-01
MeSH
Afatinib ; Antineoplastic Agents* / therapeutic use ; Antineoplastic Combined Chemotherapy Protocols / adverse effects ; Biomarkers, Tumor ; Epstein-Barr Virus Infections* / etiology ; ErbB Receptors ; Herpesvirus 4, Human ; Humans ; Nivolumab / therapeutic use ; Paclitaxel / therapeutic use ; Stomach Neoplasms* / drug therapy ; Treatment Outcome
Abstract
Purpose: This study aimed to screen targeted agents as second-line treatment with a standard-of-care (SOC) controlled umbrella trial design in advanced gastric cancer (AGC).

Patients and methods: Patients with HER2-negative AGC from eight Korean cancer centers were screened for druggable targets using immunohistochemistry (IHC) and in situ hybridization, and randomly assigned to the biomarker versus control group at a 4:1 ratio. In the biomarker group, patients were treated with specific targeted agent plus paclitaxel: pan-ERBB inhibitor for epidermal growth factor receptor (EGFR) 2+/3+ patients (afatinib; EGFR cohort), PIK3Cβ inhibitor for phosphatase and tensin homolog (PTEN) loss/null patients (GSK2636771; PTEN cohort), and anti-PD-1 inhibitor for PD-L1+, deficient mismatch repair/microsatellite instability-high, or Epstein-Barr virus-related cases (nivolumab; NIVO cohort). NONE cohort in the biomarker group without predefined biomarkers and control group received SOC (paclitaxel with or without ramucirumab). The primary end point was progression-free survival (PFS), and the secondary end points were efficacy and safety.

Results: A total of 318 patients were randomly assigned into the control (n = 64) and biomarker (n = 254; EGFR, n = 67; PTEN, n = 37; NIVO, n = 48; NONE, n = 102) groups. Median follow-up was 35 months. Median PFS and overall survival (OS) were 3.7 (95% CI, 3.1 to 4.1) and 8.6 (95% CI, 7.6 to 9.8) months in the biomarker group and 4.0 (95% CI, 3.0 to 4.6) and 8.7 (95% CI, 7.1 to 9.9) months in the control group. Afatinib addition led to marginal survival benefits to patients with EGFR 3+ compared with SOC (PFS, 4.0 v 2.2 months; P = .09), but GSK2636771 did not prolong the survival of patients with PTEN loss. Addition of nivolumab showed a durable survival benefit (median OS, 12.0 v 7.6 months; P = .08).

Conclusion: Although biomarker group did not show better survival than the control group, IHC-based screening and allocation of patients with AGC to the second-line treatment in an umbrella design were feasible for effective early screening of novel agents
Full Text
https://ascopubs.org/doi/10.1200/JCO.23.00971
DOI
10.1200/jco.23.00971
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
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/22282913/198575
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