Tesetaxel with Reduced Dose of Xeloda Improves Progression-Free Survival in Breast Cancer

Results from the phase 3 CONTESSA trial determined that patients with human epidermal growth factor receptor 2 (HER2)-negative hormone receptor (HR)-positive metastatic breast cancer treated with tesetaxel and a reduced dose of Xeloda (capecitabine) had significantly improved progression-free survival, compared with those treated with the Food and Drug Administration (FDA)-approved dose of Xeloda alone.

Tesetaxel, an oral taxane (a class of drug that blocks cell growth), is a novel drug with several unique properties including oral administration, a low pill burden (or the number of pills to take daily) and significant activity against breast cancer cell lines that are resistant to chemotherapy, according to the study, which was presented at the 2020 San Antonio Breast Cancer Symposium

“This long half-life combined with (other) features … allow for a more convenient treatment experience for patients,” said Dr. Joyce O’Shaughnessy, 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. “While the standard regimen of paclitaxel requires weekly (intravenous) infusions, tesetaxel is administered orally as two to five capsules once every three weeks.”

In the phase 3 CONTESSA trial, researchers compared tesetaxel plus Xeloda with Xeloda alone in 685 patients with HER2-negative, HR-positive metastatic breast cancer who were treated with one chemotherapy regimen for advanced disease and received a taxane either in the neoadjuvant (first therapy to shrink a tumor before administration of the main treatment) or adjuvant setting (administered after the first treatment to potentially prevent a second tumor from forming).

Patients assigned the combination treatment (343 patients) received 27 mg/m2 of tesetaxel the first day of a 21-day cycle, then 1,650 mg/m2 per day of Xeloda on days one through 14 of the same cycle. Those assigned to receive Xeloda alone (342 patients) were given the dose approved by the FDA (2,500 mg/m2 per day on days one through 14 of a 21-day cycle).

The primary end point for this study was progression-free survival (the time from treatment to disease progression). Follow-up was conducted for a median of 13.9 months.

Patients treated with tesetaxel in combination with Xeloda demonstrated a median progression-free survival of 9.8 months compared with 6.9 months in those treated with Xeloda alone.

“The increment in median (progression-free survival) is similar certainly to what we had seen in the docetaxel plus-minus (Xeloda), it was a median improvement of two months, albeit there, it was survival,” O’Shaughnessy said.

In addition, the overall response rate was 57% for the tesetaxel plus Xeloda group versus 41% for the Xeloda alone group.

Consistent with previous clinical studies, tesetaxel plus Xeloda had a manageable side effect profile. Some grade 3 or higher treatment-emergent side effects, which occurred in at least 5% of patients, were observed in more patients treated with tesetaxel plus Xeloda compared with Xeloda, including diarrhea (13.4% versus 8.9%), neutropenia (low number of neutrophils, or a type of white blood cell; 71.2% versus 8.3%), fatigue (8.6% versus 4.5%), febrile neutropenia (fever with neutropenia; 12.8% versus 1.2%), leukopenia (low white blood cell levels; 10.1% versus 0.9%), hypokalemia (low potassium levels; 8.6% versus 2.7%) and anemia (insufficient red blood cells; 8% versus 2.1%). In contrast, patients treated with Xeloda alone were more likely to develop hand-foot syndrome (swelling, redness and pain of the hands and feet) compared with those treated with tesetaxel plus Xeloda (6.8% versus 12.2%).

Side effects resulting in treatment discontinuation occurred in at least 1% of patients. Some side effects occurred more often in patients who received the combination therapy, such as neuropathy (numbness, weakness and pain in the hands and feet; 3.6% versus 0.3%) and neutropenia or febrile neutropenia (4.2% versus 1.5%), whereas others were more common in patients treated with Xeloda alone, including hand-foot syndrome (0.6% versus 2.1%) and diarrhea (0.9% versus 1.5%). Treatment discontinuation as a result from any side effect was observed in 23.1% of patients assigned combination therapy compared with 11.9% of those assigned Xeloda alone.

The combination therapy group experienced several other side effects more often than the Xeloda alone group, including grade 2 alopecia (patchy hair loss; 8% versus 0.3%) and grade 3 or greater neuropathy (5.9% versus 0.9%).

“Tesetaxel plus a reduced dose of (Xeloda) is a potential new treatment option for patients with hormone receptor positive, HER2-negative metastatic breast cancer,” O’Shaughnessy concluded.

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