KEY TAKEAWAYS
- The KX-ORAX-001 trial was a phase III study comparing oPac + E to IVpac in patients with metastatic breast cancer.
- The primary aim was to compare the confirmed radiographic response using RECIST 1.1 between oPac + E and IVpac.
- 402 patients were enrolled and randomly assigned to oPac + E or IVpac.
- oPac + E resulted in a higher confirmed response rate of 36% than IVpac 23%.
- In patients with increased liver enzymes, oPac + E caused more nausea, vomiting, diarrhea, and neutropenic consequences but less neuropathy and baldness.
Nerve damage from intravenous paclitaxel (IVpac) treatment needs premedication to prevent hypersensitivity reactions. Although oral absorption of paclitaxel is minimal, this barrier can be broken with the help of encequidar (E), a new P-glycoprotein pump inhibitor. Oral paclitaxel plus E (oPac + E) 205 mg/m2 paclitaxel plus 15 mg E methanesulfonate monohydrate three times weekly was compared to intravenous paclitaxel (IVpac) 175 mg/m2 once every three weeks in a phase III open-label research.
At least one year had passed since the last taxane for the women with metastatic breast cancer who were randomly assigned to receive either oPac + E or IVpac. Confirmed RECIST 1.1 radiographic response, as evaluated by blinded central independent review, was the major endpoint. Measures of progression-free survival (PFS) and overall survival (OS) were included as secondary end objectives.
There were 402 patients registered from Latin America (265 oPac + E, 137 IVpac), and they were evenly distributed by age, gender, and number of previous therapy. 36% of patients treated with oPac + E had a positive response, compared to 23% of patients treated with IVpac (P = .01). In terms of progression-free survival, the OS was 22.7 months compared to 16.5 months, and the hazard ratio was 0.794 (95% confidence interval [CI]: 0.607 to 1.037; P =.08), while the PFS was 8.4 months versus 7.4 months.
Five-hundred-and-four grade side effects occurred with 55% oPac + E and 53% IVpac. oPac + E was associated with increased nausea, vomiting, diarrhea, and neutropenic sequelae, especially in patients with elevated liver enzymes, but resulted in reduced rates and severity of neuropathy (2% vs 15% > grade 2) and alopecia (49% vs 62% all grades) compared to IVpac. Treatment-related fatalities occurred in 3% of oPac + E and 0% of IVpac study participants. Compared to IVpac, oPac + E improved verified tumor response, and PFS and OS showed encouraging trends. While oPac + E reduced the frequency and severity of neuropathy, it raised the risk of significant neutropenic infections. Patients with oPac + E who have baseline liver enzyme elevations are more likely to experience early neutropenia and life-threatening infections (supported by Athenex, Inc.).
Source: https://pubmed.ncbi.nlm.nih.gov/35858154/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02594371
Rugo HS, Umanzor GA, Barrios FJ, Vasallo RH, Chivalan MA, Bejarano S, Ramírez JR, Fein L, Kowalyszyn RD, Kramer ED, Wang H, Kwan MR, Cutler DL; Oraxol Study Consortium Investigators. Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous Paclitaxel in Patients With Metastatic Breast Cancer. J Clin Oncol. 2023 Jan 1;41(1):65-74. doi: 10.1200/JCO.21.02953. Epub 2022 Jul 20. PMID: 35858154; PMCID: PMC9788977.
