Dr. Lindeman on Rationale for a Phase Ib Trial of Venetoclax and Tamoxifen in Breast Cancer

Geoffrey Lindeman, MD, joint head, Stem Cells and Cancer Division at The Walter and Eliza Hall Institute of Medical Research, discusses a phase 1b dose-escalation and expansion study of the BCL-2 inhibitor venetoclax (Venclexta) combined with tamoxifen in estrogen receptor-positive and BCL-2—positive metastatic breast cancer.

Many hormone receptor-positive breast cancers also express BCL-2, which aids in cancer proliferation. Investigators reasoned that combining tamoxifen with a BCL-2 inhibitor may result in better tumor shrinkage, explains Lindeman. Venetoclax is a potent BCL-2 inhibitor that has shown a lot of promise in hematologic oncology. This is the first clinical study evaluating venetoclax in a solid tumor, he adds.

The study was a 3+3 dose escalation design, in which investigators dose escalated venetoclax up until the maximum planned tolerated dose of 800 mg. Investigators noted great tolerability across all doses, but elected to proceed with 800 mg daily as the recommended phase II dose largely due to preliminary efficacy. This also would alleviate some pill burden, says Lindeman, as the agent is delivered in the form of 100 mg tablets, and they wanted avoid patients having to take more than 8 tablets per day.