Treatment with tesetaxel plus a reduced dose of capecitabine improved progression-free survival in patients with HER2–, HR+ metastatic breast cancer compared with the FDA-approved dose of capecitabine alone.
Joyce O’Shaughnessy, MD
Treatment with tesetaxel plus a reduced dose of capecitabine (Xeloda) improved progression-free survival (PFS) in patients with human epidermal growth factor receptor 2-negative (HER2–), hormone receptor-positive (HR+) metastatic breast cancer compared with the FDA-approved dose of capecitabine alone, according to findings from the phase 3 CONTESSA trial presented during the 2020 San Antonio Breast Cancer Symposium.
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.
“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.