Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2024, Vol.27 (1), p.118-130

Ort / Verlag

Singapore: Springer Nature Singapore

Erscheinungsjahr

2024

Quelle

SpringerLink Journals

Beschreibungen/Notizen

• 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/m 2 or dose level 2, 80 mg/m 2 ) 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.