The combination of encequidar and oral paclitaxel improved the overall response rate compared with IV paclitaxel in patients with metastatic breast cancer.
Rudolf Kwan, MBBS, MRCP
The combination of encequidar and oral paclitaxel (Oral Paclitaxel regimen) improved the overall response rate (ORR) compared with IV paclitaxel in patients with metastatic breast cancer, meeting the primary endpoint of a pivotal phase III trial.
The ORR was 36% with the encequidar regimen versus 24% with IV paclitaxel (P = .01). Additionally, the rate of responders with a duration of response ≥150 days was 2.5 times greater among patients receiving encequidar plus oral paclitaxel compared to the group treated with IV paclitaxel.
“This is the second successful phase III clinical program accomplished by the clinical team this year. We are excited by the positive results in the phase III pivotal study, demonstrating improved ORR for Oral Paclitaxel compared to IV paclitaxel across a full spectrum of analyses and lower incidence of neuropathy in the Oral Paclitaxel group. We will be preparing our NDA submission as soon as possible,” Rudolf Kwan, MBBS, MRCP, chief medical officer of Athenex, the manufacturer of encequidar, said in a press release.
“We are also investigating additional indications for Oral Paclitaxel as well as combinations with other anticancer drugs, including biologics and immuno-oncology drugs. With a longer duration of response observed in this trial, we will look into the potential of this drug candidate in metronomic dosing and maintenance therapy. Based on these results, we will aggressively advance the other oral chemotherapy programs,” added Kwan.
Encequidar (formerly HM30181A) is an investigational P-gp inhibitor that enhances oral absorption, allowing drugs that are currently injectable-only to be administered orally.
The pivotal phase III trial included 402 patients with metastatic breast cancer. Patients were randomized in a 2:1 ratio to either the encequidar arm (n = 265) or IV paclitaxel (n = 137). Patient characteristics at baseline were well balanced between the 2 cohorts. The primary endpoint of ORR was confirmed via RECIST v1.1 criteria at 2 consecutive timepoints.
At the data cutoff of July 25, 2019 there was a trend toward a progression-free survival advantage with the encequidar regimen versus IV paclitaxel (P = .077). There was also a trend toward an overall survival benefit for the encequidar arm (P = .11).
Neuropathy rates were lower with encequidar plus oral paclitaxel. Across all grades, the neuropathy rate was 57% in the IV paclitaxel arm compared with 17% in the encequidar arm. The grade 3 neuropathy rates were 8% versus 1%, respectively. Rates of alopecia, arthralgia, and myalgia were also lower among patients receiving the encequidar regimen.
Overall, the rates of neutropenia were similar between both arms; however, more patients in the encequidar cohort experienced grade 4 neutropenia and infection. Gastrointestinal side effects also occurred at a higher rate among patients receiving encequidar plus oral paclitaxel.
“Based on the results of the phase III study, together with the preliminary results generated in the angiosarcoma study, Athenex believes that Oral Paclitaxel has the potential to represent a new class of oral anticancer drugs, if approved, based on the findings from this phase III study showing statistically significant improvement in ORR as monotherapy and longer duration of response over IV paclitaxel, as well as strong trends in improved PFS and OS in patients with metastatic breast cancer. There is also evidence of early onset of activity in angiosarcoma,” Johnson Lau, MD, MBBS, FRCP, chief executive officer and chairman of Athenex, said in the press release.
“Adding to this potential are the favorable safety data from this study showing lower incidence of neuropathy, which is currently a major reason for discontinuing IV paclitaxel treatment. There is a potential for Oral Paclitaxel, which is not designed to require steroid premedication for immunosuppression, to serve as a cornerstone in chemotherapy in combination with other small molecule anticancer drugs, biologics, and immuno-oncology treatment approaches, including other drug candidates in our oncology pipeline,” added Lau.
Athenex Announces Oral Paclitaxel and Encequidar had a Significantly Higher Response Rate Over IV Paclitaxel in a Phase III Pivotal Study in Metastatic Breast Cancer. Athenex, Inc. Published August 7, 2019. Accessed August 7, 2019. https://bit.ly/2OLV7gN.