Second-line chemoimmunotherapy with nivolumab and paclitaxel in immune-related biomarker-enriched advanced gastric cancer: a multicenter phase Ib/II study
- Authors
- Lee, Choong-kun; Lee, Jii Bum; Park, Se Jung; Che, Jingmin; Kwon, Woo Sun; Kim, Hyo Song; Jung, Minkyu; Lee, Seulkee; Park, Sook Ryun; Koo, Dong-Hoe; Lee, Hyun Woo; Bae, Woo Kyun; Jeung, Hei-Cheul; Hwang, In Gyu; Kim, Hyunki; Nam, Chung Mo; Chung, Hyun Cheol; Rha, Sun Young
- Issue Date
- Jan-2024
- Publisher
- Springer
- Keywords
- Advanced gastric cancer; Biomarker enriched; Immune checkpoint inhibitors; Nivolumab; Paclitaxel
- Citation
- Gastric Cancer, v.27, no.1, pp 118 - 130
- Pages
- 13
- Journal Title
- Gastric Cancer
- Volume
- 27
- Number
- 1
- Start Page
- 118
- End Page
- 130
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/71305
- DOI
- 10.1007/s10120-023-01435-9
- ISSN
- 1436-3291
1436-3305
- 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. © 2023, The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
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