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Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study

Authors
 Choong-Kun Lee  ;  Jii Bum Lee  ;  Se Jung Park  ;  Jingmin Che  ;  Woo Sun Kwon  ;  Hyo Song Kim  ;  Minkyu Jung  ;  Seulkee Lee  ;  Sook Ryun Park  ;  Dong-Hoe Koo  ;  Hyun Woo Lee  ;  Woo Kyun Bae  ;  Hei-Cheul Jeung  ;  In Gyu Hwang  ;  Hyunki Kim  ;  Chung Mo Nam  ;  Hyun Cheol Chung  ;  Sun Young Rha 
Citation
 GASTRIC CANCER, Vol.27(1) : 118-130, 2024-01 
Journal Title
GASTRIC CANCER
ISSN
 1436-3291 
Issue Date
2024-01
MeSH
Antineoplastic Combined Chemotherapy Protocols ; Biomarkers ; Epstein-Barr Virus Infections* ; Herpesvirus 4, Human ; Humans ; Immunotherapy ; Nivolumab / adverse effects ; Nivolumab / therapeutic use ; Paclitaxel ; Stomach Neoplasms*
Keywords
Advanced gastric cancer ; Biomarker enriched ; Immune checkpoint inhibitors ; Nivolumab ; Paclitaxel
Abstract
Background: We conducted a trial to evaluate the efficacy and safety of nivolumab and paclitaxel as second-line therapy for immune-related biomarker-enriched advanced gastric cancer (AGC).

Methods: This open-label, single-arm, phase Ib/II study was a part of multi-institutional, biomarker-integrated umbrella study conducted in Korea. In phase Ib, patients received nivolumab (3 mg/kg) on Days 1 and 15 and paclitaxel (dose level 1, 70 mg/m2 or dose level 2, 80 mg/m2) on Days 1, 8, 15 every four weeks. In phase II, patients with Epstein-Barr virus-related, deficient mismatch repair or programmed cell death-ligand-1-positive AGC were enrolled. The primary endpoints were recommended phase II dose (RP2D, phase Ib) and progression-free survival (PFS, phase II). Secondary endpoints included objective response rate (ORR), overall survival (OS), safety, and exploratory biomarker analysis.

Results: Dose level 2 was selected as RP2D. In phase II, 48 patients were enrolled. The median PFS and OS were 3.9 and 11.2 months, respectively. The ORR was 23.3%, and the median response duration was 16.7 months. Grade 3 or higher treatment-related adverse events, mainly neutropenia, occurred in 20 patients (41.7%). Targeted sequencing revealed that patients with RTK/RAS pathway alterations or the HLA-A02 supertype had better survival. Patients with elevated baseline interleukin-1 receptor antagonist levels had worse survival.

Conclusions: Although the study did not meet its primary end point, nivolumab and paclitaxel for AGC demonstrated a durable response with manageable toxicity profiles. Genomic analysis or plasma cytokine analysis may provide information for the selection of patients who would benefit more from immunotherapy combined with chemotherapy.
Full Text
https://link.springer.com/article/10.1007/s10120-023-01435-9
DOI
10.1007/s10120-023-01435-9
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
Kwon, Woo Sun(권우선) ORCID logo https://orcid.org/0000-0003-0268-5624
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, Jii Bum(이기쁨) ORCID logo https://orcid.org/0000-0001-5608-3157
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/22282913/198540
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