Odonate Therapeutics announced that tesetaxel, together with a reduced dose of capecitabine, improved progression-free survival in metastatic breast cancer patients taking part in a Phase 3 clinical trial.
Median progression-free survival (PFS) — the time lived until disease progression or death due to any cause — improved by 2.9 months on the combined therapy regimen as compared to capecitabine alone, rising to 9.8 months from 6.9 months.
The risk of disease progression or death fell by 28.4% on the combined regimen.
The trial, dubbed CONTESSA (NCT03326674), compared tesetaxel with a reduced dose of capecitabine (branded Xeloda, with generics available) — both administered orally — to the standard approved dose of capecitabine alone. It involved 685 patients 18 and older with human epidermal growth factor receptor 2 (HER2) negative, hormone receptor (HR) positive locally advanced or metastatic breast cancer previously treated with a taxane in the neoadjuvant (pre-surgery) or adjuvant setting.
Where indicated, participants also must have received endocrine therapy with or without a cyclin-dependent kinase (CDK) 4/6 inhibitor.
Tesetaxel is an investigational chemotherapy belonging to a class of compounds known as taxanes, widely used in cancer therapy. In contrast to other taxanes, it can be given orally and has a relatively long half-life of approximately eight days, which could enable less-frequent dosing.
Capecitabine is an oral chemotherapy medication that is considered a standard treatment in metastatic breast cancer.
In the trial, tesetaxel was given at 27 mg/m2 (27 milligrams per meter square) on the first day of each 21-day cycle. The reduced dose of capecitabine consists of 1,650 mg/m2/day for 14 days of each 21-day cycle. The standard dose of capecitabine alone (also administered orally) is 2,500 mg/m2/day for 14 days of each 21-day cycle.
“The clinically meaningful PFS improvement observed in CONTESSA, along with once-every-three-week oral dosing and low rates of clinically significant hair loss and neuropathy, could make tesetaxel an important new treatment option for patients with metastatic breast cancer,” said Andrew Seidman, MD, the trial’s co-principal investigator, in a press release.
Hair loss of at least 50% (grade two alopecia) occurred in 8% of participants treated with the combination therapy versus 0.3% in those receiving capecitabine alone.
Neuropathy (damage to the peripheral nerves) of grade three or higher occurred in nearly 6% of participants receiving both medications versus 0.9% in those receiving with capecitabine alone.
The two most frequent side effects reported for the combined therapy were a low neutrophil (a type of white blood cell) count, called neutropenia (71.2% for the combined therapy vs. 8.3% for capecitabine alone) and diarrhea (13.% vs. 8.9%).
Other side effects included: febrile neutropenia (12.8% vs. 1.2%); fatigue (8.6% vs. 4.5%); hand-foot syndrome (6.8% vs. 12.2%); low potassium, or hypokalemia (8.6% vs. 2.7%); and low white blood cell count, or leukopenia (10.1% vs. 0.9%); and anemia (8.0% vs. 2.1%).
Approximately 23% of patients taking the combined therapy stopped because of adverse events (side effects), compared to nearly 12% of those taking capecitabine alone.
Some adverse events were associated with stopping treatment. The most common, seen in at least 1% of patients, were: neutropenia or febrile neutropenia (4.2% for tesetaxel plus capecitabine vs. 1.5% for capecitabine alone); neuropathy (3.6% vs. 0.3%); diarrhea (0.9% vs. 1.5%); and hand-foot syndrome (0.6% vs. 2.1%).
Although overall survival data are not ready, an interim analysis reportedly showed no negative effects on this measure. A final overall survival analysis is expected in 2022.
“Tesetaxel represents a potential important clinical advance for patients with metastatic breast cancer,” said Joyce O’Shaughnessy, MD, the trial’s other co-principal investigator. “There remains a significant unmet medical need for novel therapies that offer quality-of-life advantages for patients with metastatic breast cancer.”
CONTESSA is being conducted at 180 investigational sites in 18 countries in North America, Europe and Asia. Odonate plans to present the trial results at an upcoming medical meeting.
“We look forward to working closely with global regulatory authorities to make tesetaxel available to patients with metastatic breast cancer. We plan to submit a New Drug Application for tesetaxel to the [U.S. Food and Drug Administration] in mid-2021,” said Kevin Tang, Odonate’s CEO.