SABCS 2020: Novel Oral Taxane Demonstrates Efficacy in CONTESSA Trial

By Kate O’Rourke

An all-oral regimen of tesetaxel plus a reduced dose of capecitabine significantly improved progression-free survival (PFS) and other endpoints, compared with capecitabine alone, in patients with HER2-negative, hormone receptor (HR)-positive metastatic breast cancer (MBC), according to findings from the CONTESSA trial.

These results, from the phase 3 CONTESSA trial, were presented at the 2020 San Antonio Breast Cancer Symposium (Abstract GS4-01). In the trial, patients had previously received no more than one chemotherapy regimen for advanced disease and a taxane in the neoadjuvant or adjuvant setting.

“Tesetaxel is a new chemical entity that unlike the other taxanes, paclitaxel and docetaxel, is not effluxed by the PGP pump, and 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,” said Joyce O’Shaughnessy, MD, Co-Chair of Breast Cancer Research and Chair of Breast Cancer Prevention Research at Baylor-Sammons Cancer Center, who presented the research. “Tesetaxel plus a reduced dose of capecitabine is a potential new treatment option for patients with HR-positive, HER2-negative MBC.”

Tesetaxel is a novel, oral taxane with several properties that make it unique, including oral administration with a low pill burden; an 8-day terminal plasma half-life in humans, enabling once every 3-weeks dosing; no observed hypersensitivity reactions; and significant activity against chemotherapy-resistant breast cancer cell lines.

In CONTESSA, which enrolled 685 patients and randomized them 1-to-1, the median PFS was 9.8 months for tesetaxel plus a reduced dose of capecitabine, compared with 6.9 months for capecitabine alone (Hazard Ratio, 0.716; P=0.003).

The objective response rate was increased in the tesetaxel arm (57% vs. 41%; P=0.0002), as was the 24-week disease control rate (67% vs. 50%; P less than 0.0001). The overall survival data are immature.

To be eligible for the trial, patients could have received any number of prior endocrine therapies and any number of prior targeted therapies such as CDK4/6 inhibitors. Patients were required to have measurable disease per RECIST 1.1 or bone only disease with a lytic component.

The combination of tesetaxel and capecitabine was associated with a manageable side effect profile, which was consistent with previous clinical studies. Grade 3 or higher treatment-emergent adverse events that occurred in at least 5% of patients included neutropenia (70.9% for tesetaxel plus capecitabine vs. 8.3% for capecitabine alone), diarrhea (13.1% vs. 8.9%), hand‐foot syndrome (6.8% vs. 12.2%), febrile neutropenia (13.1% vs. 1.2%), fatigue (8.6% vs. 4.5%), hypokalemia (8.6% vs. 2.7%), leukopenia (9.8% vs. 0.9%), and anemia (8.0% vs. 2.4%).

Treatment discontinuation due to any adverse event was more common in the tesetaxel cohort (23.1% vs. 11.9%).

There were six treatment-related deaths in the tesetaxel plus capecitabine arm and three treatment-related deaths in the capecitabine-only arm. Tesetaxel dose reductions occurred in 76% of patients, primarily due to neutropenia.

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