medwireNews: The addition of the orally administered taxane tesetaxel to reduced-dose capecitabine achieves a significant progression-free survival (PFS) benefit in individuals with hormone receptor (HR)-positive, metastatic breast cancer who have previously received a taxane, suggest phase 3 trial findings.
Presenter Joyce O'Shaughnessy (Baylor University Medical Center, Dallas, Texas, USA) told delegates of the 2020 San Antonio Breast Cancer Symposium that tesetaxel plus reduced-dose capecitabine represents “a potential new treatment option” for these patients.
She explained that unlike paclitaxel and docetaxel, tesetaxel is not effluxed by the P-glycoprotein pump in the gastric system, and therefore has “the unique feature of being intrinsically orally bioavailable,” along with having “a much longer half-life.”
The CONTESSA study enrolled 685 patients with HR-positive, HER2-negative disease who had previously received a taxane in the neoadjuvant or adjuvant setting. Participants could have received any number of prior endocrine or approved targeted therapies (around 50% had received CDK4/6 inhibitors), but no more than one prior chemotherapy regimen for metastatic disease.
After a median follow-up of 13.9 months, median PFS – as assessed by independent review – was 9.8 months for the 343 patients who received oral tesetaxel 27 mg/m2 on day 1 of each 21-day cycle alongside oral capecitabine 1650 mg/m2 on days 1–15.
This was significantly longer than the median PFS of 6.9 months achieved by their 342 counterparts who instead received oral capecitabine 2500 mg/m2 on days 1–15 of every cycle, and equated to a significant hazard ratio for progression or death of 0.716.
“The treatment effect was similar across protocol-specified subgroups,” including participants with a disease-free interval of less than 24 months following prior taxane therapy and those who had received CDK4/6 inhibitors, said O'Shaughnessy.
The objective response rate and the disease control rate at 24 weeks were both significantly higher with tesetaxel plus capecitabine than capecitabine alone, at 57% versus 41% and 67% versus 50%, respectively.
Overall survival data were not mature at the time of data cutoff, and the final analysis is expected in 2022, reported the presenter.
In terms of the safety profile, the most frequent grade 3 or 4 treatment-emergent adverse events (AEs) in the combination versus capecitabine alone groups were neutropenia (70.9 vs 8.3%), febrile neutropenia (13.1 vs 1.2%), and diarrhea (13.1 vs 8.9%).
O'Shaughnessy also highlighted that grade 2 alopecia occurred in 8.0% of combination-treated patients compared with 0.3% of those given capecitabine alone, but there were no treatment-related hypersensitivity reactions.
A total of 23.1% of participants in the tesetaxel arm and 11.9% of those in the control arm discontinued treatment due to any AE, most commonly due to neutropenia or febrile neutropenia (4.2%) in the tesetaxel group and hand–foot syndrome (2.1%) in the control group. The corresponding rates of treatment-related deaths were 1.8% and 0.9%.
medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group