Paclitaxel oral solution vs injection, 2L gastric cancer

Background

Multicenter, open-label, randomized phase 3 trial in China (53 centers) evaluating a paclitaxel oral solution (RMX3001) against conventional IV paclitaxel as second-line therapy for advanced gastric cancer. N=536 patients with unresectable, recurrent, or metastatic gastric adenocarcinoma progressing after fluoropyrimidine-based first-line chemotherapy. Randomization was 1:1, stratified by prior gastrectomy, ECOG performance status, and prior chemotherapy. Oral paclitaxel is formulated to permit gastrointestinal absorption without the Cremophor EL vehicle required for IV administration, potentially avoiding hypersensitivity reactions and premedication while removing the need for infusion visits.

Results

Interventions and follow up: Arm A: Paclitaxel oral solution 200 mg/m² twice daily on days 1, 8, and 15 of a 28-day cycle (n=268)
Arm B: Paclitaxel injection 175 mg/m² IV on day 1 of a 21-day cycle (n=268)
Primary endpoint: Dual primary — BIRC-assessed PFS (noninferiority margin HR 1.18) and OS (noninferiority margin HR 1.16)
mFollow up: NR
Results: OS: 9.13 vs 6.54 mo, HR 0.770 (95.5% CI, 0.635-0.934), P=.006 — noninferiority met and superiority demonstrated
PFS (BIRC): 3.02 vs 2.89 mo, HR 0.894 (95% CI, 0.719-1.112), P=.311 — noninferiority met
ORR: NR in the abstract

Adverse events

Overall: Favorable and manageable safety profile with oral solution versus injection
Neurologic: Lower incidence of peripheral neuropathy with oral solution
Hypersensitivity: Lower incidence with oral solution (no Cremophor EL vehicle)
Other: Less alopecia, less fatigue, and fewer musculoskeletal and connective tissue disorders with oral solution
Treatment-related fatal AEs: 4 (1.5%) vs 3 (1.1%)
Grade ≥3 (any): NR in the abstract

Conclusions

A paclitaxel oral solution was noninferior to IV paclitaxel for PFS and unexpectedly produced a statistically significant OS advantage (9.13 vs 6.54 months, HR 0.770) in second-line advanced gastric cancer, with less neuropathy, less hypersensitivity, and less alopecia. This is the first phase 3 evidence that an oral taxane formulation can match and in this trial exceed the survival delivered by the intravenous parent drug in this setting. It offers a chemotherapy option that removes infusion-chair time and steroid/antihistamine premedication.

Key Limitations

Open-label design, which can influence subsequent-therapy decisions and the timing of progression assessment even though PFS was BIRC-reviewed. The OS superiority arose in a trial designed for noninferiority, so the survival gain is a favorable but hypothesis-generating finding rather than a prespecified superiority result, and the mechanism for a nearly 3-month OS advantage without a corresponding PFS difference is unexplained — differential tolerability, dose intensity, and post-progression therapy are all plausible contributors and were not reported in the abstract. The trial was conducted entirely in China, where second-line gastric cancer practice, patient body habitus, and taxane pharmacokinetics may differ from Western populations. Median follow-up, ORR, and detailed grade ≥3 toxicity rates were not reported in the abstract, and the twice-daily oral schedule depends on adherence and food-effect control.

Clinical Context

Second-line paclitaxel, usually with ramucirumab, has been a global standard for advanced gastric cancer since RAINBOW, and NCCN, ASCO, and ESMO all list a taxane-based second-line regimen as preferred. Paclitaxel oral solution (RMX3001, Haihe Biopharma) has been approved by China's NMPA for second-line gastric cancer; it is not FDA- or EMA-approved, and this trial did not include ramucirumab, so it does not directly displace paclitaxel plus ramucirumab where that combination is available. Its practical relevance is greatest where infusion capacity is constrained or where hypersensitivity or neuropathy limits IV taxane use, and it establishes proof of concept for oral taxane delivery that other agents in development are pursuing.

References