Immune checkpoint inhibitors plus paclitaxel-based chemotherapy vs. oxaliplatin-based therapy as first-line treatment for patients with HER2-negative unresectable or metastatic gastric/gastroesophageal junction cancer: results of a multicenter retrospective study.

Abstract

Background: For unresectable or metastatic gastric/gastroesophageal junction cancer (G/GEJC), immune checkpoint inhibitors (ICIs) plus platinum-based doublet chemotherapy [FOLFOX (leucovorin, fluorouracil, and oxaliplatin) and XELOX (capecitabine and oxaliplatin)] are currently recommended as the standard first-line treatment. Research indicates that ICIs combined with paclitaxel have a synergistic effect, but the evidence is insufficient. This multicenter, retrospective study aimed to compare the efficacy and tolerability of ICIs [mainly anti-programmed cell death-1 (anti-PD-1) antibodies] plus a paclitaxel-based chemotherapy regimen (ICIs plus PTX) vs. an oxaliplatin-based regimen (ICIs plus OXA) as the first-line therapy for advanced G/GEJC.

Methods: This research involved 123 patients with advanced G/GEJC at three institutions in China from August 2019 to June 2022. The ICIs plus PTX group included 58 patients, whereas the ICIs plus OXA group included 65 patients. We compared the efficacy and safety of two treatment regimens.

Results: Fifty-eight patients (47.2%) received ICIs plus PTX, and 65 patients (52.8%) received ICIs plus OXA. The median progression-free survival (PFS) [8.07 vs. 7.23 months; hazard ratio (HR) =0.845; 95% confidence interval (CI): 0.568-1.257; P=0.40] and overall survival (OS) (14.83 vs. 15.10 months; HR =0.852; 95% CI: 0.536-1.355; P=0.50) were not significantly different between the ICIs plus PTX group and the ICIs plus OXA group. The objective response rate (ORR) (50.0% vs. 53.8%, P=0.67) and disease control rate (DCR) (98.3% vs. 93.8%, P=0.21) were also similar between the PTX and OXA groups, and both treatments exhibited manageable side effects. Subgroup analysis based on patient characteristics suggested that PFS HRs favored the ICIs plus PTX subgroup in patients aged <65 years or without liver metastasis.

Conclusions: In summary, ICIs plus PTX are as effective as ICIs plus OXA for treating advanced G/GEJC with manageable toxicity. The advantages of ICIs plus PTX in terms of adverse events (AEs) may support it as an alternative to ICIs plus OXA.