Study: Oral Tesetaxel, Reduced Dose Capecitabine Improved Progression-Free Survival in Patients with HER2-Negative HR-Positive Metastatic Breast Cancer
Tesetaxel is a novel, oral taxane with several unique properties being investigated for use in patients with HER2-negative, HR-positive metastatic breast cancer.
New research presented at the 2020 Virtual San Antonio Breast Cancer Symposium has found that an all-oral regimen of tesetaxel plus a reduced dose of capecitabine significantly improved progression-free survival in patients with human epidermal growth factor receptor 2 (HER2)-negative, hormone receptor (HR)-positive metastatic breast cancer compared to treatment with capecitabine alone.
The CONTESSA trial is a multinational, multicenter, randomized, phase 3 registration study comparing tesetaxel and a reduced dose of capecitabine to the approved dose of capecitabine alone in patients with HER2-negative, HR-positive metastatic breast cancer who have received no more than 1 chemotherapy regimen for advanced disease and have received a taxane in the neoadjuvant setting. It has enrolled 685 patients.
Tesetaxel is a novel, oral taxane with several unique properties, including oral administration with a low pill burden, an 8-day terminal plasma half-life enabling dosing once every 3 weeks, no observed hypersensitivity reactions, and significant activity against chemotherapy-resistant breast cancer cell lines. More than 1000 patients have received the drug in clinical trials, and it has had encouraging monotherapy activity in a phase 2 study of 38 patients with HER2-negative, HR-positive metastatic breast cancer.
The CONTESSA trial met the primary endpoint of improved progression-free survival (PFS) with a median PFS of 9.8 months for tesetaxel plus a reduced dose of capecitabine compared with 6.9 months for capecitabine alone. The overall response rate (ORR) was 57% for the combination therapy compared with 41% for capecitabine alone, and overall survival data are immature, according to the authors.
Tesetaxel plus capecitabine was associated with a manageable adverse effect (AE) profile, with grade 3 or higher treatment-emergent AEs (TEAEs) occurring in 5% or more of patients. These AEs included neutropenia, diarrhea, hand-foot syndrome, febrile neutropenia, fatigue, hypokalemia, leukopenia, and anemia. TEAEs resulting in treatment discontinuation occurred in 1% or more of patients, and included neutropenia or febrile neutropenia, neuropathy, diarrhea, and hand-foot syndrome.
Treatment discontinuation due to any AE occurred in 23.1% of patients treated with tesetaxel plus capecitabine versus 11.9% of patients treated with capecitabine alone. Grade 2 alopecia occurred in 8% of patients treated with tesetaxel plus capecitabine, compared with 0.3% of patients who received capecitabine alone. Grade 3 or higher neuropathy occurred in 5.9% of patients treated with the combination therapy compared with 0.9% of patients treated with capecitabine monotherapy.
Based on these results, the authors concluded that the all-oral regimen of tesetaxel and a reduced dose of capecitabine significantly improved PFS compared to capecitabine alone. Neutropenia was the most common grade 3 or higher TEAE, and rates of clinically significant alopecia and neuropathy were low.
Shaughnessy J, 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. Presented at: 2020 Virtual San Antonio Breast Cancer Symposium. Accessed December 8, 2020.