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Open-Label, Randomized, Multicenter, Phase III Study Comparing Oral Paclitaxel Plus Encequidar Versus Intravenous
Hope S Rugo1, Gerardo A Umanzor2, Francisco J Barrios3
1University of California San Francisco, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.
Summary
Oral paclitaxel with encequidar (oPac + E) demonstrated a higher confirmed tumor response compared to intravenous paclitaxel (IVpac) in metastatic breast cancer patients. While oPac + E showed reduced neuropathy, it increased neutropenic infections, especially in patients with elevated liver enzymes.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Intravenous paclitaxel (IVpac) administration is associated with neuropathy and requires premedication for hypersensitivity reactions.
- Oral paclitaxel absorption is poor; encequidar (E), a P-glycoprotein pump inhibitor, enhances oral bioavailability.
Purpose of the Study:
- To compare the efficacy and safety of oral paclitaxel plus encequidar (oPac + E) versus intravenous paclitaxel (IVpac) in women with metastatic breast cancer.
Main Methods:
- A phase III open-label study randomized 402 patients with metastatic breast cancer to receive either oPac + E (205 mg/m² paclitaxel + 15 mg E) for 3 consecutive days weekly or IVpac (175 mg/m²) every 3 weeks.
- The primary endpoint was confirmed radiographic response by RECIST 1.1. Secondary endpoints included progression-free survival (PFS) and overall survival (OS).
Main Results:
- The confirmed response rate was significantly higher for oPac + E (36%) compared to IVpac (23%) (P = .01).
- Progression-free survival (PFS) showed a favorable trend for oPac + E (8.4 months vs. 7.4 months; P = .046).
- oPac + E resulted in lower incidence and severity of neuropathy and alopecia but increased nausea, vomiting, diarrhea, and neutropenic complications, particularly in patients with elevated liver enzymes.
Conclusions:
- Oral paclitaxel plus encequidar (oPac + E) achieved a higher confirmed tumor response than IVpac, with trends toward improved PFS and OS.
- oPac + E demonstrated a reduced incidence of neuropathy but an increased risk of neutropenic infections, especially in patients with pre-existing elevated liver enzymes.
