A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric canceropen access
- Authors
- Lee, CK[Lee, Choong-kun]; Rha, SY[Rha, Sun Young]; Kim, HS[Kim, Hyo Song]; Jung, M[Jung, Minkyu]; Kang, B[Kang, Beodeul]; Che, J[Che, Jingmin]; Kwon, WS[Kwon, Woo Sun]; Park, S[Park, Sejung]; Bae, WK[Bae, Woo Kyun]; Koo, DH[Koo, Dong-Hoe]; Shin, SJ[Shin, Su-Jin]; Kim, H[Kim, Hyunki]; Jeung, HC[Jeung, Hei-Cheul]; Zang, DY[Zang, Dae Young]; Lee, SK[Lee, Sang Kil]; Nam, CM[Nam, Chung Mo]; Chung, HC[Chung, Hyun Cheol]
- Issue Date
- 12-Oct-2022
- Publisher
- NATURE PORTFOLIO
- Citation
- NATURE COMMUNICATIONS, v.13, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- NATURE COMMUNICATIONS
- Volume
- 13
- Number
- 1
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/101665
- DOI
- 10.1038/s41467-022-33267-z
- ISSN
- 2041-1723
- 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. In patients with advanced gastric cancer (AGC), resistance to treatment with trastuzumab and cytotoxic chemotherapy remains high. Here, the authors report the results of a phase Ib/II clinical trial assessing the safety and clinical response to a quadruplet regimen of pembrolizumab, trastuzumab, capecitabine, and cisplatin as a first-line therapy for HER2-positive AGC.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - Medicine > Department of Medicine > 1. Journal Articles
![qrcode](https://api.qrserver.com/v1/create-qr-code/?size=55x55&data=https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/101665)
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.