한빛사논문
- 조회938
Choong-kun Lee , MD, PhD1,2; Hyo Song Kim , MD, PhD1,2; Minkyu Jung , MD, PhD1,2; Hyunki Kim, MD, PhD3; Woo Kyun Bae , MD, PhD4; Dong-Hoe Koo , MD, PhD5; Hei Cheul Jeung, MD, PhD6; Sook Ryun Park, MD, PhD7; In Gyu Hwang , MD, PhD8; Dae Young Zang , MD, PhD9; Hyun Woo Lee , MD10; Sejung Park, PhD2; Chung Mo Nam, PhD11; Hyun Cheol Chung , MD, PhD1,2; and Sun Young Rha, MD, PhD1,2,12
1Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
2Sondang Institute for Cancer Research, Yonsei University College of Medicine, Seoul, South Korea
3Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
4Department of Hematology-Oncology, Chonnam National University Medical School and Hwasun Hospital, Hwasun, South Korea
5Division of Hematology and Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea
6Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
7Division of Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
8Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, South Korea
9Division of Hematology-Oncology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, South Korea
10Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, South Korea
11Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, South Korea
12Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea
Corresponding author : Sun Young Rha, MD, PhD
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.
논문정보
- Research article
- 2023년 10월 (BRIC 등록일 2023-11-13)
- 국내 연구진
- 의약학 > 종양의학
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