Response rate, survival superior with oral paclitaxel versus IV in metastatic breast cancer

Created by oncoXchange

February 2020



By Wayne Kuznar for oncoXchange

An oral form of paclitaxel together with a specific inhibitor of ap-glycoprotein was superior to IV paclitaxel on the endpoints of confirmed response and overall survival (OS), with minimal clinically significant neuropathy, in a phase III trial of patients with metastatic breast cancer, according to data presented at the 2019 San Antonio Breast Cancer Symposium.

In the open-label randomized study, in the prespecified modified intent-to-treat population (mITT), patients who received oral paclitaxel and encequidar had a confirmed response rate of 40.4% versus 25.6% who received IV paclitaxel (P = 0.005).

In the ITT analysis, 35.8% of the group randomized to oral paclitaxel and encequidar had a confirmed tumor response, compared with 23.4% in the IV paclitaxel group (P = 0.011).

“Oral paclitaxel and encequidar provides an important oral therapeutic option for patients with metastatic breast cancer, representing a meaningful improvement in the clinical profile of paclitaxel,” said the study’s lead investigator, Gerardo Antonio Umanzor Funez, MD, medical oncologist with Centro Oncologico Integral, who conducted the study with DEMEDICA of San Pedro Sula, Honduras.

Ongoing analysis of progression-free survival (PFS) shows a strong trend in the protocol prespecified mITT population in favor of oral paclitaxel and encequidar, with a median of 9.3 months, compared with 8.3 months in the group randomized to IV paclitaxel (P = 0.0760).

Ongoing analysis of OS in the mITT population significantly favored oral paclitaxel and encequidar, with a median OS of 27.9 months in this group versus 16.5 months in the IV paclitaxel group (HR, 0.684; 95% CI, 0.475-0.985; P = 0.02).

In the ITT population, the medians were 27.7 and 16.9 months, respectively, a difference that failed to achieve significance (HR, 0.762; 95% CI, 0.540-1.077; P = 0.114).

Oral paclitaxel and encequidar is comprised of 30-mg capsules of solubilized paclitaxel and a 15-mg tablet of encequidar, which is an ap-glycoprotein pump inhibitor that allows the oral paclitaxel to be absorbed into the bloodstream. Compliance with the oral regimen was good, said Dr. Umanzor.

The dosing of the oral form is equivalent to mg/m2 of IV paclitaxel weekly, but with lower peak of the drug concentration, he told OncoXchange. A lower peak concentration should translate to fewer side effects, which was borne out in this clinical trial.

A total of 402 metastatic breast cancer patients were enrolled into the trial. The patients were randomly assigned in a 2:1 ratio to receive either 205 mg/m² of oral paclitaxel plus encequidar 3 days a week, or 175 mg/m²paclitaxel intravenously every 3 weeks. Their tumors were evaluated for response and confirmed at two consecutive blinded evaluations by a blinded, independent radiology company.

The prespecified mITT population consisted of 360 patients who had a baseline evaluable scan and had received at least seven doses of oral paclitaxel or one dose of IV paclitaxel.

In 51% of the oral paclitaxel/encequidar group who had a confirmed response, the response lasted > 150 days, compared with 38% of the IV paclitaxel group who had a response.

The rate of neuropthay grade ≥2 was remarkably lower with oral paclitaxel plus encequidar compared with paclitaxel (7.6% vs. 31.1%, respectively).

The rate of alopecia ≥2 was also lower in the oral paclitaxel/encequidar arm at 28.8% versus the IV paclitaxel arm at 48.1%. The rate of neutropenia grade ≥3 was similar between the two arms. Diarrhea grade ≥3 was higher in the oral paclitaxel/encequidar group versus the IV paclitaxel group (5.3% vs. 1.5%, respectively), as was the rate of vomiting or nausea ≥3 (6.9% vs. 0.7%, respectively).