Hope S. Rugo, MD
In a Latin American phase III trial reported in the Journal of Clinical Oncology, Hope S. Rugo, MD, and colleagues found that oral paclitaxel with the P-glycoprotein pump inhibitor encequidar produced a higher response rate and trends toward better survival outcomes vs intravenous (IV) paclitaxel in patients with metastatic breast cancer.
As stated by the investigators, “Intravenous paclitaxel … is complicated by neuropathy and requires premedication to prevent hypersensitivity-type reactions. Paclitaxel is poorly absorbed orally; encequidar, a novel P-glycoprotein pump inhibitor, allows oral absorption.”
In the open-label trial, 402 patients with ≥ 1 year since their last taxane treatment from sites in 10 countries in Central/South America and the Caribbean were randomly assigned 2:1 between December 2015 and February 2019 to receive oral paclitaxel at 205 mg/m2 plus encequidar methanesulfonate monohydrate at 15 mg for 3 consecutive days per week (n = 265) or IV paclitaxel at 175 mg/m2 once every 3 weeks. The primary endpoint was confirmed radiographic objective response on blinded independent central review.
Confirmed objective response was observed in 95 patients (35.8%; complete response in 3 [1%]) in the oral paclitaxel group vs 34 patients (23.4%; complete response in 1 [< 1%]) in the IV paclitaxel group (P = .01). Median durations of response were 36 weeks (range = 6–111+ weeks) vs 33 weeks (range = 4–84+ weeks).
Median progression-free survival was 8.4 months vs 7.4 months (hazard ratio [HR] = 0.768, 95.5% confidence interval [CI] = 0.584–1.01, P = .046). Median overall survival was 22.7 months vs 16.5 months (HR = 0.794, 95.5% CI = 0.607–1.037, P = .08).
Grade 3 or 4 adverse events occurred in 55% of the oral paclitaxel group vs 53% of the IV paclitaxel group. The IV paclitaxel group had higher rates of grade ≥ 2 neuropathy (15% vs 2%) and any grade alopecia (62% vs 49%). The oral paclitaxel group had higher rates of gastrointestinal adverse events (overall = 85% vs 51% any grade, grade 3–4 in 12% vs 4%), including nausea, vomiting, and diarrhea. The incidence of grade ≥ 3 neutropenia was similar in the two groups (36% vs 32%), but grade 4 neutropenia was more common in the oral paclitaxel group (15% vs 9%); treatment was discontinued due to neutropenia in 7% vs 1% of patients.
Adverse events led to death in 8% vs 9% of patients; however, death due to infectious complications considered related to treatment occurred in 9 (3%) vs 0 patients. A post hoc multivariate analysis in the oral paclitaxel group to determine risk of grade 4 or 5 toxicities during the first 10 weeks of therapy showed that increasing baseline bilirubin and gamma-glutamyltransferase and decreasing albumin were associated with increased risk of severe neutropenia and infectious complications.
The investigators concluded: “[Oral paclitaxel plus encequidar] increased the confirmed tumor response versus IV [paclitaxel], with trends in [progression-free survival] and [overall survival]. Neuropathy was less frequent and severe with [oral paclitaxel plus encequidar]; neutropenic serious infections were increased. Elevated liver enzymes at baseline predispose [oral paclitaxel plus encequidar] patients to early neutropenia and serious infections.”
Dr. Rugo, of UCSF Helen Diller Family Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by Athenex, Inc. For full disclosures of the study authors, visit ascopubs.org.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.