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.

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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.

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 study exploring RANK ligand as a target for breast cancer prevention in patients who harbor the 

One of the areas of interest is understanding how normal cells communicate with each other in breast cancer, Lindeman explains. This might lead to an understanding of the cells that give rise to breast cancer. The progenitor cells, he adds, are known as the culprit cells that give rise to 

Results of a study showed that the progenitor cells contained a RANK-positive and a RANK-negative population. The RANK-positive population is likely the cell of origin that gives rise to tumors in 

 carriers, Lindeman says. By switching these cells off using a RANK ligand inhibitor, Lindeman says that this has the potential to be a prevention strategy of breast cancer in patients with 

View more from the 2016 San Antonio Breast Cancer Symposium

Geoffrey Lindeman, MD, joint head, Stem Cells and Cancer Division at The Walter and Eliza Hall Institute of Medical Research, discusses a study exploring RANK ligand as a target for breast cancer prevention in patients who harbor the BRCA1 mutation.

Geoffrey Lindeman, MD

Articles

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

Dr. Lindeman on RANK Ligand as Breast Cancer Prevention Target in BRCA1 Carriers