Oral Paclitaxel Outperforms IV in OS for Advanced Gastric Cancer

Gastric/GEJ tumor: ©LASZLO - stock.adobe.com

Data from a phase 3 clinical trial (CTR20190050), presented at the 2025 Gastrointestinal Cancers Symposium, demonstrated that the oral solution of paclitaxel (Liporaxel) was non-inferior to the intravenous (IV) solution in progression-free survival (PFS) for second-line advanced gastric cancer. However, oral paclitaxel showed superior overall survival (OS) compared with the IV formulation.

In total, 536 eligible participants were randomized to receive either the oral solution of paclitaxel (n = 268) or the IV formulation (n = 268) of the agent, between April 22, 2019, and the data cut-off of January 31, 2022. The study met non-inferiority criteria for PFS, with a blind independent review committee (BIRC)–assessed median PFS of 3.02 months (95% CI, 2.69-3.71) in the oral paclitaxel group compared with 2.89 months (95% CI, 2.53-3.48) in the IV group (HR, 0.894; 95% CI, 0.719-1.112; p = .311).

Furthermore, with a primary analysis cut-off of February 15, 2023, OS showed superiority with the paclitaxel oral solution, with a median OS of 9.13 months (95% CI, 7.72-10.97) vs 6.54 months (95% CI, 5.75-7.26) in the IV group, showing a 2.59-month improvement (HR, 0.770; 95.5% CI, 0.635-0.934; p = 0.006). Notably, the median follow-up of was 13.4 months in the oral group and 12.6 months in the IV group.

“Paclitaxel oral solution demonstrated non-inferiority in PFS and superiority in OS compared [with] paclitaxel IV, with clinically manageable and favorable safety profile, supporting paclitaxel oral solution as a second-line treatment option for gastric cancer,” Jin Li, MD, PhD, of the Department of Medical Oncology, Tongji University Shanghai East Hospital, and co-authors, wrote in the abstract describing their poster presentation.

Although IV paclitaxel is a category 1 preferred regimen in the second-line treatment of gastric cancer, there remains unmet needs with this treatment approach including vehicle-led safety risk, long time injection, premedication, or frequent hospital visits. However, the oral solution of paclitaxel—the world's first successfully developed oral formulation of the agent, according to the abstract—may serve as an alternative to investigate this new formulation of the standard of care approach. Investigators sought to investigate paclitaxel oral solution vs paclitaxel IV as a second-line monotherapy in order to establish non-inferiority in efficacy and comparable safety profile for patients with gastric cancer.

Investigators conducted this randomized, open-label, non-inferiority clinical trial at 53 centers in China, evaluating patients with unresectable, recurrent, or metastatic gastric cancer which had progressed following treatment with fluoropyrimidine- or fluoropyrimidine plus platinum-based first-line therapy. Eligible participants were stratified by gastrectomy, ECOG performance status, and prior chemotherapy, and were randomly assigned 1:1 to receive an oral solution of paclitaxel at 200mg/m² twice daily on days 1, 8, and 15 of a 28-day cycle or IV paclitaxel at 175mg/m² on day 1 of a 21-day cycle.

The co-primary end points of the trial were PFS assessed by blind independent review committee (BIRC) and OS, with non-inferiority margin of hazard ratio (HR) of 1.18 for PFS and 1.16 for OS, according to the abstract.

Regarding safety, the oral solution of paclitaxel was clinically manageable and had a favorable safety profile vs the IV formulation, supporting paclitaxel oral solution as a second-line treatment option for gastric cancer, authors wrote.

Treatment-related adverse effects (TRAEs) in the oral administration group had a lower incidence of all-grade neuropathy vs the IV group (22.3% vs 38.7%); alopecia, fatigue, musculoskeletal, and connective tissue disorders all occurred at a lower incidence in the oral group, and no hypersensitivity occurred without premedication. The authors of the abstract noted that the most common grade 3 or higher TRAEs were neutrophil count decrease (oral group, 47.9%; IV, 54.5%), white blood cell count decrease (41.5%; 35.3%) and anemia (16.6%; 10.9%). Although grade 5 TRAEs were rare, they had comparable rates across both groups (1.5%; 1.1%).

Reference

Li J, Huang M, Deng T, et al. Paclitaxel oral solution versus paclitaxel injection as a second-line therapy in advanced gastric cancer: A randomized, open-label, non-inferiority phase 3 trial. J Clin Oncol. 2025;43(suppl 4):442. doi:10.1200/JCO.2025.43.4_suppl.442.