Oral paclitaxel regimen improves outcomes vs. IV formulation in metastatic breast cancer
SAN ANTONIO — A novel combination of oral paclitaxel plus encequidar significantly improved overall response rates compared with IV paclitaxel among women with metastatic breast cancer, according to results of a randomized phase 3 study presented at San Antonio Breast Cancer Symposium.
“We wanted to have an oral taxane agent available that we knew to be safe and widely used [for patients with] breast cancer,” Gerardo Antonio Umanzor Funez, MD, medical oncologist with Centro Oncologico Integral in Buenos Aires, Argentina, told Healio. “We knew with previous preclinical studies of the oral formulation that we could achieve a lower peak concentration of paclitaxel. We hypothesized that — if we had this lower peak concentration — we could reduce the side effects for patients, but with the same pharmacokinetic exposure or better. We wanted better results with fewer side effects.”
Researchers developed an orally administered version of paclitaxel made bioavailable when combined with encequidar (Athenex), a novel, highly specific, potent P-glycoprotein pump inhibitor that increases absorption of oral paclitaxel.
The open-label trial included 402 patients with metastatic breast cancer.
Researchers randomly assigned them 2:1 to 205 mg/m² oral paclitaxel plus 15 mg encequidar (n = 265) three times weekly or 175 mg/m² IV paclitaxel (n = 137) every 3 weeks. Demographics appeared well-balanced between the oral and IV treatment groups, similar proportions of which had received prior taxane therapy (28% vs. 31%).
Radiologically confirmed tumor responses — including complete and partial responses — at two consecutive timepoints served as the primary endpoint. PFS and OS served as secondary endpoints.
Researchers powered the study to confirm tumor response rates based upon a modified intent-to-treat population of 360 patients with target tumors that could be evaluated per RECIST version 1.1 criteria by central review, including 240 patients who had received at least seven doses of the oral combination and 120 patients who received at least one dose of IV paclitaxel.
In the intent-to-treat population, investigators reported confirmed tumor response rates of 35.8% with oral paclitaxel plus encequidar and 23.4% with IV paclitaxel, for a difference of 12.4% (P = .011).
Confirmed ORRs in the modified intent-to-treat population were 40.4% with oral paclitaxel plus encequidar vs. 25.6% with IV paclitaxel, which represented an absolute improvement of 14.8% (P = .005).
Median duration of confirmed response was 39 weeks with the oral paclitaxel combination vs. 30.1 weeks with IV paclitaxel. About half of patients in the oral paclitaxel group (51%) achieved confirmed responses that exceeded 150 days, compared with 38% in the IV paclitaxel group.
Results of ongoing analyses of the modified intent-to-treat population showed longer median PFS (9.3 months vs. 8.3 months) and OS (27.9 months vs. 16.9 months; P = .035) with the oral combination.
Oral paclitaxel plus encequidar appeared associated with lower overall incidence of neuropathy (17% vs. 57%) and grade 3 neuropathic symptoms (1% vs. 8%) compared with IV paclitaxel. However, incidence of gastrointestinal adverse events was higher with the oral combination.
Future research will examine the tolerability of the oral combination among patients at high risk for peripheral neuropathy, Umanzor Funez said.
“We are always excited to have new treatments for our patients, and any time that we are able to give our patients an oral agent that can be administered at home, it is a positive thing,” Umanzor Funez told Healio. “There can be a quality-of-life issue for many of our patients in terms of having to travel to the clinic to receive their treatment infusion. We always want to have more options for our patients, so having oral paclitaxel — which is active and provides increased OS — is a significant accomplishment.” – by Jennifer Southall
Umanzor Funez GA, et al. Abstract GS6-01. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-14, 2019; San Antonio.
Disclosures: Athenex supported the study. Umanzor Funez reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.