Author: By Shreeya Nanda, Senior medwireNews Reporter
medwireNews: Patients who have received prior taxane therapy for hormone receptor-positive, HER2-negative metastatic breast cancer may benefit from treatment with the oral taxane tesetaxel alongside reduced-dose capecitabine, say the CONTESSA investigators.
Reporting the findings at the 2020 San Antonio Breast Cancer Symposium, Joyce O'Shaughnessy, from Baylor University Medical Center in Dallas, Texas, USA, explained that unlike the other taxanes, tesetaxel efflux is not mediated by the gastric P-glycoprotein pump, and thus the agent has “the unique feature of being intrinsically orally bioavailable.”
Tesetaxel also has “a much longer half-life” than docetaxel or paclitaxel, and can therefore be administered once every 21 days compared with every 7 days for paclitaxel, she commented.
For the phase III trial, Joyce O'Shaughnessy and colleagues recruited 685 individuals from centres in North America, Europe or Asia–Pacific who had received prior taxane in the neoadjuvant or adjuvant setting and one or fewer lines of chemotherapy in the metastatic setting. The majority (>90%) had previously received endocrine therapy and approximately half had been treated with CDK4/6 inhibitors.
During a median follow-up of 13.9 months, the primary endpoint of independently reviewed progression-free survival (PFS) was a median of 9.8 months for the participants who were randomly assigned to receive oral tesetaxel 27 mg/m2 on day 1 together with oral capecitabine 1650 mg/m2 on days 1–15 of every 21-day cycle.
By comparison, median PFS was 6.9 months for the patients who instead received oral capecitabine 2500 mg/m2 on days 1–15 of each cycle, giving a significant hazard ratio for progression or death of 0.716 in favour of the combination.
Joyce O'Shaughnessy noted that “the treatment effect was similar across protocol-specified subgroups, including patients with a disease-free interval less than 24 months following neoadjuvant or adjuvant taxane therapy, patients who had been previously treated with a CDK4/6 inhibitor and patients in each geographic region.”
Patients in the combination group achieved a significantly higher objective response rate and 24-week disease control rate than those in the capecitabine monotherapy group, at 57% versus 41% and 67% versus 50%, respectively.
The overall survival results were immature at data cutoff and the final analysis is expected in 2022, said the presenter.
Neutropenia was the most common treatment-emergent adverse event (AE) of grade 3 or 4 in the combination versus control arm, observed in 70.9% and 8.3% of patients, respectively, followed by febrile neutropenia (13.1 vs 1.2%) and diarrhoea (13.1 vs 8.9%). No patient experienced a treatment-related hypersensitivity reaction.
The rate of discontinuation due to AEs was 23.1% for patients given tesetaxel plus reduced-dose capecitabine and 11.9% for those given capecitabine alone, while treatment-related deaths occurred in 1.8% and 0.9%, respectively.
The presenter therefore concluded that the all-oral regimen of “tesetaxel plus reduced-dose capecitabine is a potential new treatment option for patients with hormone receptor-positive, HER2-negative metastatic breast cancer.”
Abstract GS4-01. O'Shaughnessy J, Schwartzberg L, Piccart M, et al. Results from CONTESSA: A phase 3 study of tesetaxel plus a reduced dose of capecitabine versus capecitabine alone in patients with HER2-, hormone receptor + (HR+) metastatic breast cancer (MBC) who have previously received a taxane. 2020 San Antonio Breast Cancer Symposium; 8–11 December.
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