December 11, 2020 - Patients with human epidermal growth factor receptor 2-negative, hormone receptor-positive metastatic breast cancer who were treated with tesetaxel and a reduced dose of capecitabine experienced improvements in progression-free survival compared with those treated with the FDA-approved dose of capecitabine alone.
Patients with human epidermal growth factor receptor 2-negative (HER2–), hormone receptor-positive (HR+) metastatic breast cancer who were treated with tesetaxel and a reduced dose of capecitabine (Xeloda) experienced improvements in progression-free survival (PFS) compared with those treated with the FDA-approved dose of capecitabine alone, according to results from the phase 3 CONTESSA trial.
Tesetaxel, an oral taxane, is a novel drug with several unique properties including oral administration and significant activity against breast cancer cell lines that are resistant to chemotherapy, according to results presented at the 2020 San Antonio Breast Cancer Symposium.
“Tesetaxel …is a new chemical entity that, unlike the other taxanes, paclitaxel and docetaxel, is not effluxed by the P-gp pump,” said Joyce O’Shaughnessy, MD, co-chair of breast cancer research and chair of breast cancer prevention research at Baylor-Sammons Cancer Center, during the virtual presentation of the study results. “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.”
O’Shaughnessy added that tesetaxel also has a low pill burden compared with other treatments. “While the standard regimen of paclitaxel requires weekly IV infusions, tesetaxel is administered as 2 to 5 capsules once every 3 weeks,” she said.
In the phase 3 CONTESSA trial, researchers compared tesetaxel plus capecitabine with capecitabine alone in 685 patients with HER2–, HR+ metastatic breast cancer treated with 1 chemotherapy regimen for advanced disease and received a taxane either in the neoadjuvant or adjuvant setting. Patients assigned to the combination regimen (n = 343; median age, 56 years) received 27 mg/m2 of tesetaxel the first day of a 21-day cycle, then 1,650 mg/m2 per day of capecitabine on days 1 through 14 of the same cycle. Those assigned to capecitabine alone (n = 342; median age, 57 years) received the dose approved by the FDA (2,500 mg/m2 per day on days 1 through 14 of a 21-day cycle).
“The reason for the combination versus monotherapy is because it was designed as a registration trial, very similar to the initial docetaxel plus-minus [capecitabine], paclitaxel plus-minus gemcitabine,” O’Shaughnessy said. “The other thing is that it did allow in a more virulent population, it didn’t have any requirement for at least a year of disease-free interval, so patients could come on within a year of finishing up their taxane.”
The primary end point for this study was PFS. Follow-up was conducted for a median of 13.9 months.
Patients assigned tesetaxel with capecitabine demonstrated a median PFS of 9.8 months, compared with 6.9 months in those assigned capecitabine alone, which led to an improvement of 2.9 months (HR, 0.716; 95% CI, 0.573-0.895; P = .003).
“The increment in median PFS is similar certainly to what we had seen in the docetaxel plus-minus [capecitabine],” O’Shaughnessy said. “It was a median improvement of 2 months, albeit there, it was survival. We’ll have to wait and see. Probably we’re going to be using a doublet for patients who have virulent disease who really need a response.”
In addition, the overall response rate was 57% for the tesetaxel plus capecitabine group versus 41% for the capecitabine alone group (P = .0002). Data on overall survival were immature at the time of this analysis.
Consistent with previous clinical studies, tesetaxel plus capecitabine had a manageable adverse event (AE) profile. Some grade 3 or higher treatment-emergent AEs, which occurred in at least 5% of patients, were observed in more patients assigned tesetaxel plus capecitabine, compared with capecitabine, including diarrhea (13.4% vs 8.9%), neutropenia (71.2% vs 8.3%), fatigue (8.6% vs 4.5%), febrile neutropenia (12.8% vs 1.2%), leukopenia (10.1% vs 0.9%), hypokalemia (8.6% vs 2.7%), and anemia (8% vs 2.1%). In contrast, patients assigned capecitabine alone were more likely to develop hand-foot syndrome compared with those assigned tesetaxel plus capecitabine (6.8% vs 12.2%).
AEs resulting in treatment discontinuation occurred in at least 1% of patients. Some events occurred more often in patients assigned to the combination therapy such as neuropathy (3.6% vs 0.3%) and neutropenia or febrile neutropenia (4.2% vs 1.5%), whereas others were more common in patients assigned capecitabine alone including hand-foot syndrome (0.6% vs 2.1%) and diarrhea (0.9% vs 1.5%). Treatment discontinuation as a result from any AE was observed in 23.1% of patients assigned combination therapy compared with 11.9% of those assigned capecitabine alone.
The combination therapy group experienced several other AEEs more often than the capecitabine alone group, including grade 2 alopecia (8% vs 0.3%) and grade 3 or greater neuropathy (5.9% 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 concluded.
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. Presented at: 2020 San Antonio Breast Cancer Symposium; December 8-11, 2020; Virtual. Abstract GS4-01.