GI AEs Associated With Oral Paclitaxel Plus Encequidar Subside with Antiemetics, Loperamide in Metastatic Breast Cancer

December 11, 2020 - Gastrointestinal adverse events that occurred in patients with metastatic breast cancer who were treated with oral paclitaxel and encequidar can be managed by the use of 5- HT3 inhibitors and early intervention with loperamide.

Gastrointestinal (GI) adverse events (AEs) that occurred in patients with metastatic breast cancer who were treated with oral paclitaxel and encequidar can be managed by the use of 5- HT3 inhibitors and early intervention with loperamide, according to research presented at the 2020 San Antonio Breast Cancer Symposium.

This combination regimen allows for fewer AEs, but investigators looked to find a way to prevent GI AEs that were found to be higher following treatment with oral paclitaxel and encequidar.

“Paclitaxel is substrate of the intestinal e-flux pump p-glycoprotein that leads to low oral bioavailbailty. Encequidar is a specific p-glycoprotein absorbed by patients to help bioavailbailty,” explained lead investigator Hope Rugo, MD, from the University California San Francisco Helen Diller Family Comprehensive Cancer Center, in a poster presentation at SABCS. “This avoids the need for Cremophor risk and allows for at home dosing with patients and eliminates the need for IV infusions.” However, she added, the incidence of gastrointestinal adverse events from this combination was high.

The researchers investigated preventive measures for GI AEs associated with oral paclitaxel and encequidar or IV paclitaxel – which were evaluated in a multinational trial looking at the safety of this combination in 442 patients.

Patients were randomized 2:1 on either oral paclitaxel and encequidar (205mg/m2/day x3 weekly) or IV paclitaxel (175 mg/m2 every three weeks) until disease progression or toxicity. The primary end point of the study was efficacy as defined by tumor response with secondary endvpoints of progression-free survival (PFS) and overall survival (OS).

All patients on IV paclitaxel (n = 111) were given dexamethasone and antihistamine premedication and after 30% (n = 70) of patients were enrolled to include those on oral paclitaxel and encequidar the protocol was amended to address the imbalance of GI AEs. Treatments included loperamide taken at home at the onset of diarrhea along with prophylactic anti-emetic therapy.

The most frequently prescribed anti-emetic therapies included ondanesteron, granisetron, palenosetron, aprepitant, metoclopramide, domperidone, and aprepitant. The majority of patients in the combination (59%) and monotherapy (54%) arms received ondanesteron.

After the amended use of prophylactic anti-emetic therapy, there was a marked decrease of grade 2 or higher vomiting and diarrhea in patients on oral paclitaxel and encequidar, from 24% to 7% and 27% to 16% respectively. A greater incidence of both AEs were seen in patients treated with IV paclitaxel.

Of note, prior to the amendment, overall GI AEs occurred less frequently in patients on IV paclitaxel compared to the combination regimen, with a rate of only 1% of grade 3 vomiting and diarrhea occurring. Grade 3 incidences prior to the amended treatment in patients on the oral regimen were 7% in vomiting and 9% in diarrhea, showing a slight decrease to 4% and 3%, respectively.

Reference

Rugo H, Umanzor G, Barrios F J et al. Oral paclitaxel and encequidar (oPac+E) in the treatment of metastatic breast cancer (mBC): management of gastrointestinal adverse events (GI AE). Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual.