Reduced-dose nanoparticle albumin-bound-paclitaxel combined with ramucirumab as second-line treatment for advanced gastric cancer: a multicenter phase II study

Abstract Background Weekly paclitaxel combined with ramucirumab is the standard second-line chemotherapy regimen for advanced gastric cancer. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is increasingly used as it lowers the risk of hypersensitivity reactions; however, full-dose nab-paclitaxel (100 mg/m²) combined with ramucirumab frequently leads to severe myelosuppression. In clinical practice, dose reduction is often required, particularly in older patients or those with a poor performance status. However, the clinical efficacy and safety of a reduced-dose regimen of nab-paclitaxel combined with ramucirumab have not yet been prospectively evaluated. Accordingly, this multicenter phase II study aimed to assess the efficacy and tolerability of reduced-dose nab-paclitaxel combined with ramucirumab as second-line treatment for advanced gastric cancer. Methods This open-label, single-arm, multicenter phase II trial was conducted at nine institutions between March 2018 and August 2021 and enrolled 50 patients with unresectable or recurrent gastric or esophagogastric junction adenocarcinoma who had previously undergone treatment with fluoropyrimidine-based chemotherapy. Nab-paclitaxel (80 mg/m²) was administered intravenously on days 1, 8, and 15 in combination with ramucirumab (8 mg/kg) on days 1 and 15 of each 28-day cycle. The primary endpoint was progression-free survival. The secondary endpoints included overall survival, response rate, disease control rate, relative dose intensity, and safety. Tumor responses were assessed using the Response Evaluation Criteria in Solid Tumors v1.1. Results The median progression-free survival was 5.8 months (95% confidence interval [CI], 4.6–7.0). The median overall survival was 12.5 months (95% CI, 10.6–14.5). Among patients with measurable lesions, the objective response rate was 33.3%, including one case of complete response. The disease control rate was 80%. Grade ≥ 3 neutropenia occurred in 50% of patients, whereas febrile neutropenia occurred in 2%. The relative dose intensity was 86.5% for nab-paclitaxel and 92.8% for ramucirumab. Conclusions Reduced-dose nab-paclitaxel combined with ramucirumab demonstrated modest efficacy and favorable tolerability as second-line chemotherapy for advanced gastric cancer. This regimen may represent a practical treatment alternative for patients deemed unsuitable for full-dose nab-paclitaxel due to concerns regarding its toxicity. Trial registration This study was registered in the UMIN Clinical Trials Registry on February 14, 2018 (UMIN000031285).