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

4051 Background: Paclitaxel injection (paclitaxel IV) is category 1 preferred regimen in the second-line therapy of gastric cancer. Safer and more convenient paclitaxel oral solution (Liporaxel), the world’s first oral formulation, has been initially approved in Korea for treatment of gastric cancer. This study aimed to determine non-inferiority in efficacy and safety profile of paclitaxel oral solution versus paclitaxel IV, as monotherapy in larger population with unresectable locally advanced, recurrent or metastatic gastric cancer in China. 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 1:1 (stratified by gastrectomy, ECOG PS and prior chemotherapy) to receive oral paclitaxel (200mg/m 2 twice daily on days 1, 8, 15 every 4 weeks) or paclitaxel IV (175mg/m 2 on day 1 every 3 weeks). The co-primary endpoints were blind independent review committee (BIRC)-assessed progression-free survival (PFS) and overall survival (OS), with non-inferiority margin of hazard ratio (HR) of 1.18 and 1.16 in statistical comparison, respectively. Results: From April 22, 2019, to January 31, 2022 (data cut-off), 536 patients were randomized to oral paclitaxel (n=268) or paclitaxel IV (n=268), with median follow-up of 13.4 vs. 12.6 months, respectively. The PFS showed non-inferiority of oral paclitaxel to paclitaxel IV with median BIRC-assessed PFS 3.02 months (95% confidence interval CI: 2.69, 3.71) in oral paclitaxel vs. 2.89 months (95% CI: 2.53, 3.48) in paclitaxel IV (HR 0.894, 95% CI: 0.719, 1.112, p=0.311). The OS (cutoff on February 15, 2023) showed superiority of oral paclitaxel over paclitaxel IV with median OS 9.13 months (95% CI: 7.72, 10.97) in oral paclitaxel vs. 6.54 months (95% CI: 5.75, 7.26) in paclitaxel IV (HR 0.770, 95.5% CI: 0.635, 0.934, p=0.006). For the treatment-related adverse events (TRAEs), oral paclitaxel decreased neuropathy incidence (22.3% vs. 38.7% all grade) and no hypersensitivity occurred in oral paclitaxel without premedication. The most common ≥Grade 3 TRAEs were neutrophil count decreased (47.9% in oral paclitaxel vs. 54.5% in paclitaxel IV), white blood cell count decreased (41.5% vs. 35.3%) and anemia (16.6% vs. 10.9%). Grade 5 TRAEs were at low with comparable incidences (four 1.5% vs. three 1.1%). Conclusions: The study showed statistical non-inferiority of paclitaxel oral solution in PFS and statistically significant and clinically meaningful improvement in OS as compared to paclitaxel IV, with clinically manageable safety profile, supporting paclitaxel oral solution as second-line treatment option for patients with gastric cancer. Clinical trial information: CTR20190050.