Paclitaxel oral solution versus paclitaxel injection as second-line therapy for advanced gastric cancer: a multicenter, open-label, randomized phase III trial

Abstract

Background Paclitaxel is widely used in various cancers. This study aimed to evaluate paclitaxel oral solution versus paclitaxel injection in the second line of gastric cancer. Patients and methods Patients with unresectable, recurrent, or metastatic disease who have progressed after fluoropyrimidine-based first-line therapy were randomly assigned 1:1 (stratified by gastrectomy, Eastern Cooperative Oncology Group performance status and prior chemotherapy) to receive paclitaxel oral solution (200 mg/m2 twice daily on days 1, 8, and 15 of a 28-day cycle) or paclitaxel injection (175 mg/m2 on day 1 of a 21-day cycle). Dual primary endpoints included progression-free survival (PFS), assessed by a blind independent review committee, and overall survival (OS), with the noninferiority margin of the hazard ratio (HR) of 1.18 for PFS and 1.16 for OS. Results A total of 536 patients were randomly assigned into two groups (n = 268 each). Compared with paclitaxel injection, paclitaxel oral solution demonstrated a statistically significant and clinically meaningful improvement in OS [9.13 versus 6.54 months; HR 0.770, 95.5% confidence interval (CI) 0.635-0.934, P = 0.006], and was noninferior to paclitaxel injection in PFS (3.02 versus 2.89 months; HR 0.894, 95% CI 0.719-1.112, P = 0.311), along with a favorable and manageable safety profile. Paclitaxel oral solution showed a lower incidence of neuropathy, hypersensitivity reactions, alopecia, and musculoskeletal and connective tissue disorders. Treatment-related fatal adverse events were rare in both groups [four (1.5%) versus three (1.1%)]. Conclusions These findings support the use of paclitaxel oral solution as a viable alternative second-line option for gastric cancer.