Intraperitoneal paclitaxel plus intravenous fluorouracil, leucovorin, oxaliplatin (FOLFOX) and nivolumab for gastric cancer with peritoneal metastasis: results from the IPLUS Phase II study

Abstract

Background Gastric cancer with peritoneal metastasis (PM) carries a poor prognosis, with median overall survival (mOS) of 9-11 months using standard systemic chemotherapy. Intraperitoneal (IP) chemotherapy has shown promise, but its effect still remains unclear. This study aims to show the efficacy and safety of IP paclitaxel with systemic FOLFOX +/- nivolumab in gastric cancer patients with PM. Methods This single-arm, open-label Phase II IPLUS trial evaluated biweekly IP paclitaxel (60 mg/m(2)) plus systemic FOLFOX +/- nivolumab in 22 patients with histologically confirmed gastric cancer and PM, aged 20-80 years, and no other hematogenous metastasis. Co-primary endpoints were one-year OS and progression-free survival (PFS) rate, with secondary endpoints including mOS, median PFS (mPFS), response rates, conversion surgery rate, and safety per CTCAE v5.0. Results From January 2021 to August 2022, 22 patients received a mean of 16.0 +/- 13.6 cycles. One-year OS and PFS rates were 86.4% and 63.6%, respectively, with mOS of 20.2 months (95% CI 17.2-32.9) and mPFS of 13.1 months (95% CI 12.2-25.7). Conversion surgery was achieved in 40.9%, with mOS of 32.9 months for the conversion surgery group. Of patients with measurable lesion, RECIST v1.1 responses (n = 5) showed an objective response rate of 40.0% and disease control rate of 80.0%. Conclusion IP paclitaxel plus FOLFOX +/- nivolumab demonstrates encouraging survival outcomes and tolerability in gastric cancer with PM with high conversion surgery rates.