The following article features coverage from the 2019 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Oral paclitaxel with encequidar appeared to be have the same if not better clinical benefit than intravenous paclitaxel for patients with metastatic breast cancer, according to the results of the phase 3 randomized clinical trial (ClinicalTrials.gov identifier: NCT02594371) presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas.

“Paclitaxel is a substrate of the intestinal efflux pump P-glycoprotein, P-gp, resulting in a low oral bioavailability of paclitaxel,” explained the study’s lead investigator, Gerardo Antonio Umanzor Funez, MD, medical oncologist at Centro Oncologico Integral, who conducted the study with DEMEDICA of San Pedro Sula, Honduras.

“Encequidar is a minimally absorbed, highly specific potent inhibitor of P-gp that increases the absorption of oral paclitaxel,” he said. 

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The trial enrolled 402 patients with metastatic breast cancer, excluding those with brain metastases. Patients were randomly assigned in a 2 to 1 fashion to receive either oral paclitaxel with encequidar 205 mg/m2 for 3 days a week or intravenous paclitaxel 175 mg/m2 every 3 weeks. Patients were instructed to take encequidar first, followed by 1 hour of fasting, and then oral paclitaxel.


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The trial met its primary end point, showing that in a prespecified modified intent-to-treat population of 360 patients, the radiologically confirmed response rate was significantly higher for oral paclitaxel with encequidar compared with intravenous paclitaxel (39.1% vs 24.8%; P =.005). 

However, the higher response rate can largely be attributed to a higher partial response rate (39.1% vs 24.8%). The complete response rate was similar between oral paclitaxel with encequidar and intravenous paclitaxel (1.3% vs 0.8%).

Further, the responses appeared to be durable. Three-quarters of patients with confirmed tumor responses who received oral paclitaxel maintained a response beyond 100 days and 12.6% maintained a response beyond 300 days. 

In an ongoing analysis of progression-free survival, the modified intent-to-treat population favored oral paclitaxel with encequidar over intravenous paclitaxel (hazard ration [HR], 0.760; 95% CI, 0.551-1.049; P =.0773), as well as overall survival (HR, 0.684; 95% CI, 0.475-0.985; P =.0353).

As for the safety profile, patients who received oral paclitaxel with encequidar had lower rates of neuropathy both overall (17% vs 57%) and for grade 3 severity (1% vs 8%) compared with intravenous paclitaxel. 

However, oral paclitaxel with encequidar had higher rates of neutropenia, anemia, urinary tract infection, and gastrointestinal adverse events. In particular, the incidence of diarrhea (24.2% vs 8.1%), nausea (23.1% vs 5.2%), vomiting (17.0% vs 4.4%), and abdominal pain (13.6% vs 4.4%) were considerably higher for oral paclitaxel with encequidar compared with intravenous paclitaxel.  

“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,” Dr Umanzor Funez concluded.

Reference

  1. Umanzor G, Cutler DL, Barrios FJ, et al. Oral paclitaxel with encequidar: The first orally administered paclitaxel shown to be superior to IV paclitaxel on confirmed response and survival with less neuropathy: A phase III clinical study in metastatic breast cancer. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS6-01.