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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.
- Source :
-
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association [Gastric Cancer] 2024 Jan; Vol. 27 (1), pp. 118-130. Date of Electronic Publication: 2023 Oct 31. - Publication Year :
- 2024
-
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).<br />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/m <superscript>2</superscript> or dose level 2, 80 mg/m <superscript>2</superscript> ) 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.<br />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.<br />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.<br /> (© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.)
Details
- Language :
- English
- ISSN :
- 1436-3305
- Volume :
- 27
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
- Publication Type :
- Academic Journal
- Accession number :
- 37906316
- Full Text :
- https://doi.org/10.1007/s10120-023-01435-9