Tesetaxel-capecitabine may provide all-oral option for metastatic breast cancer subset
Click Here to Manage Email Alerts
The addition of tesetaxel to reduced-dose capecitabine improved PFS among women with HER2-negative, hormone receptor-positive metastatic breast cancer, according to study results presented at the virtual San Antonio Breast Cancer Symposium.
These data from the phase 3 CONTESSA trial suggest tesetaxel (Odonate Therapeutics) plus capecitabine might serve as an all-oral regimen for women who previously received a taxane, according to the researchers.
“Chemotherapy regimens that offer robust efficacy while preserving patient quality of life are needed for metastatic breast cancer,” Joyce A. O’Shaughnessy, MD, co-chair of breast cancer research and chair of breast cancer prevention research at Baylor Charles A. Sammons Cancer Center and for The US Oncology Network, said during her presentation.
Tesetaxel — a novel oral taxane with an every-3-week dosing schedule — demonstrated encouraging activity as monotherapy in a phase 2 trial of patients with hormone receptor-positive, HER2-negative metastatic breast cancer, she added.
“Tesetaxel, unlike the other taxanes, paclitaxel and docetaxel, is not effluxed by the P-glycoprotein pump,” O’Shaughnessy said. “As a result, tesetaxel has the unique feature of being intrinsically orally bioavailable. It is also significantly more soluble than the other taxanes and has a much longer half-life. ... These features allow for a more convenient treatment experience for patients. [Whereas] the standard regimen of paclitaxel requires weekly IV infusions, tesetaxel is administered orally as two to five capsules once every 3 weeks.”
The analysis included 685 women with hormone receptor-positive, HER2-negative, metastatic breast cancer who received no more than one chemotherapy regimen for advanced disease and who received a taxane in the neoadjuvant or adjuvant setting. About 90% of the women had previously received endocrine therapy, and about half had received a CDK 4/6 inhibitor.
O’Shaughnessy and colleagues randomly assigned the women to receive 27 mg/m2 tesetaxel on day 1 of a 21-day cycle plus a reduced dose of capecitabine at 1,650 mg/m2 daily on days 1 through 14 (n = 343; median age, 56 years), or capecitabine alone at the approved dose of 2,500 mg/m2 daily on days 1 through 14 (n = 342; median age, 57 years).
PFS, assessed by an independent radiologic review committee, served as the study’s primary endpoint. Secondary endpoints included OS, objective response rate and disease control rate.
Median follow-up was 13.9 months.
Results showed the tesetaxel combination conferred a 2.9-month improvement in median PFS, which met statistical significance (9.8 months vs. 6.9 months; HR = 0.71; 95% CI, 0.57-0.89). This treatment effect appeared similar across patient subgroups, including among women with a disease-free interval of less than 24 months following prior taxane therapy (HR = 0.7; 95% CI, 0.48-1.02) and women who had been previously treated with a CDK 4/6 inhibitor (HR = 0.76; 95% CI, 0.55-1.04).
Women assigned tesetaxel plus capecitabine also showed a significantly higher ORR (57% vs. 41%; P = .0002) and 24-week disease control rate (67% vs. 50%; P < .0001).
OS data were immature at the time of the analysis and are not expected until 2022, O’Shaughnessy said.
The most common adverse events of any grade included neutropenia (tesetaxel plus capecitabine, 76.9% vs. capecitabine alone, 22.6%), hand-foot syndrome (50.7% vs. 66.2%), nausea (62.6% vs. 42.7%) and diarrhea (61.1% vs. 46.9%).
The most frequent grade 3 or worse adverse event associated with tesetaxel plus capecitabine was neutropenia (grade 3, 32.6%; grade 4, 38.3%) — which was generally manageable with dose reductions and granulocyte colony-stimulating factor, O’Shaughnessy said — and with capecitabine alone was hand-foot syndrome (grade 3, 12.2%).
Women in the tesetaxel-plus-capecitabine group had a higher rate of discontinuation due to adverse events (23.1% vs. 11.9%) and treatment-related death (1.8% vs. 0.9%).
“Tesetaxel plus a reduced dose of capecitabine is a potential new treatment option for patients with hormone receptor-positive, HER2-negative metastatic breast cancer,” O’Shaughnessy said.
Regarding whether the 2.9-month difference in PFS was clinically meaningful, O’Shaughnessy said the data are similar to what had been seen with the addition of docetaxel to capecitabine, although OS data will be needed to confirm this comparison.
“We’re probably going to be using a doublet for patients who have virulent disease and who really need a response, and the response rate of 57% is probably enough to say we would utilize a doublet such as this for patients with more virulent disease,” she said. “I think it parallels docetaxel-capecitabine or gemcitabine-paclitaxel, it’s just that it gives patients now an all-oral option.”
Collapse
O’Shaughnessy J, et al. Abstract GS4-01. Presented at: San Antonio Breast Cancer Symposium (virtual meeting); Dec. 8-11, 2020.
Click Here to Manage Email Alerts