Paclitaxel oral solution versus paclitaxel injection as a second-line therapy in advanced gastric cancer: A randomized, open-label, non-inferiority phase 3 trial.

442 Background: Paclitaxel injection (paclitaxel IV) is category 1 preferred regimen in the second-line therapy of gastric cancer, while it has shortcomings including vehicle-led safety risk, long time injection, premedication or frequent hospital visit. Paclitaxel oral solution (Liporaxel), the world's first successfully developed oral formulation, is an alternative. This study aimed to establish non-inferiority in efficacy and comparable safety profile of paclitaxel oral solution versus paclitaxel IV, as a second-line monotherapy in gastric cancer. Methods: This is a randomized, open-label, non-inferiority phase 3 trial conducted at 53 centers in China. Patients with unresectable or recurrent or metastatic gastric cancer progressed after fluoropyrimidine- or fluoropyrimidine plus platinum-based first-line therapy were randomly assigned at 1:1 ratio (stratified by gastrectomy, ECOG PS and prior chemotherapy) to receive paclitaxel oral solution (200mg/m 2 twice daily on days 1, 8, 15 of a 28-day cycle) or paclitaxel IV (175mg/m 2 on day 1 of a 21-day cycle). Co-primary endpoints were progression-free survival (PFS) assessed by blind independent review committee (BIRC) and overall survival (OS), with non-inferiority margin of hazard ratio (HR) of 1.18 for PFS and 1.16 for OS. Results: From April 22, 2019, to January 31, 2022 (data cut-off), 536 patients were randomized to receive either paclitaxel oral solution (n=268) or paclitaxel IV (n=268), with a median follow-up of 13.4 vs. 12.6 months. PFS met non-inferiority criteria, with BIRC-assessed median PFS of 3.02 months (95% confidence interval [CI]: 2.69, 3.71) in the oral group vs. 2.89 months (95% CI: 2.53, 3.48) in the IV group (HR=0.894, 95% CI: 0.719, 1.112, p =0.311). OS (cut-off on February 15, 2023, for OS primary analysis) demonstrated superiority for paclitaxel oral solution, with median OS of 9.13 months (95% CI: 7.72, 10.97) vs. 6.54 months (95% CI: 5.75, 7.26), showing 2.59-month improvement (HR=0.770, 95.5% CI: 0.635, 0.934, p =0.006). For the treatment-related adverse events (TRAEs), the oral group showed lower incidences of neuropathy (22.3% vs. 38.7% all grade), alopecia, fatigue, musculoskeletal and connective tissue disorders, and no hypersensitivity occurred without premedication. The most common ≥Grade 3 TRAEs were neutrophil count decreased (47.9% in oral vs. 54.5% in IV), white blood cell count decreased (41.5% vs. 35.3%) and anemia (16.6% vs. 10.9%). Grade 5 TRAEs were rare with comparable rates across two groups (four [1.5%] vs. three [1.1%]). Conclusions: Paclitaxel oral solution demonstrated non-inferiority in PFS and superiority in OS compared to paclitaxel IV, with clinically manageable and favorable safety profile, supporting paclitaxel oral solution as a second-line treatment option for gastric cancer. Clinical trial information: CTR20190050.