Dr. Jin Li and colleagues conducted a phase 3 clinical trial to evaluate the efficacy and safety of paclitaxel oral solution compared to paclitaxel injection as a second-line treatment for advanced gastric cancer. Paclitaxel injection (IV) is a widely used treatment in this setting, but its administration presents several challenges, including vehicle-related safety risks, prolonged infusion times, the need for premedication, and frequent hospital visits. To address these limitations, paclitaxel oral solution (Liporaxel), the world’s first successfully developed oral formulation, was introduced as a potential alternative. The aim of this study was to determine whether paclitaxel oral solution could demonstrate non-inferior progression-free survival (PFS) while offering a comparable safety profile, with the additional advantage of an oral route of administration.Methods
The study was conducted across 53 medical centers in China and included patients with unresectable, recurrent, or metastatic gastric cancer who had experienced disease progression after fluoropyrimidine- or fluoropyrimidine plus platinum-based first-line therapy. Participants were randomly assigned in a 1:1 ratio to receive either paclitaxel oral solution or paclitaxel IV, with stratification based on prior gastrectomy, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and previous chemotherapy.
Patients in the paclitaxel oral solution group received 200 mg/m² twice daily on days 1, 8, and 15 of a 28-day cycle, while those in the paclitaxel IV group received 175 mg/m² on day 1 of a 21-day cycle. The study’s co-primary endpoints were progression-free survival (PFS) and overall survival (OS). PFS was assessed by an independent, blinded review committee (BIRC), and the pre-specified non-inferiority margins were set at a hazard ratio (HR) of 1.18 for PFS and 1.16 for OS.
Results
Between April 22, 2019, and January 31, 2022, a total of 536 patients were enrolled and randomized, with 268 patients assigned to each treatment group. The median follow-up duration was 13.4 months for the oral solution group and 12.6 months for the IV group.
The study successfully met the non-inferiority criteria for progression-free survival. The median PFS in the paclitaxel oral solution group was 3.02 months (95% confidence interval [CI]: 2.69, 3.71), compared to 2.89 months (95% CI: 2.53, 3.48) in the IV group. The hazard ratio for PFS was 0.894 (95% CI: 0.719, 1.112, p=0.311), indicating comparable efficacy between the two treatment arms.
Overall survival analysis demonstrated superiority for the oral formulation. The median OS was 9.13 months (95% CI: 7.72, 10.97) in the paclitaxel oral solution group, compared to 6.54 months (95% CI: 5.75, 7.26) in the IV group, reflecting a 2.59-month improvement. The hazard ratio for OS was 0.770 (95.5% CI: 0.635, 0.934, p=0.006), favoring the oral formulation.
Safety and Adverse Events
Treatment-related adverse events (TRAEs) were analyzed across both groups. Neuropathy occurred at a lower incidence in the oral group (22.3%) compared to the IV group (38.7%). The oral formulation was also associated with lower incidences of alopecia, fatigue, and musculoskeletal and connective tissue disorders. Notably, hypersensitivity reactions were absent in the oral group and did not require premedication.
The most common Grade 3 or higher TRAEs included neutrophil count decrease, which occurred in 47.9% of patients in the oral group versus 54.5% in the IV group. White blood cell count decreased in 41.5% of oral group patients compared to 35.3% in the IV group. Anemia was observed in 16.6% of patients receiving the oral formulation, compared to 10.9% in the IV group. Grade 5 TRAEs were rare and occurred at comparable rates between the two groups, with four cases (1.5%) in the oral group and three cases (1.1%) in the IV group.
Discussion and Conclusion
The results of this phase 3 trial, led by Dr. Jin Li and colleagues, demonstrate that paclitaxel oral solution is a viable and potentially superior alternative to paclitaxel IV as a second-line treatment for advanced gastric cancer. The study successfully established non-inferiority in PFS, confirming that the oral formulation is as effective as IV paclitaxel in delaying disease progression. Additionally, the oral formulation demonstrated superiority in OS, providing a significant survival advantage.
Beyond its efficacy, the oral formulation offered an improved safety profile, particularly in reducing neuropathy and hypersensitivity reactions. Its manageable safety profile, coupled with the convenience of oral administration and reduced need for hospital visits, makes paclitaxel oral solution an attractive treatment option for patients with advanced gastric cancer.
