Aggressive Breast Cancer Type Shows Response to New 'Smart Drug'

The new class of smart drugs has the ability to bring the toxic payload directly to the cancer cells.

A new smart drug may become a viable option for patients with metastatic triple-negative breast cancer who have undergone 2 or more previous treatment options, according to a clinical trial at New York-Presbyterian/Columbia University’s Herbert Irving Comprehensive Cancer Center.

The drug, sacituzumab govitecan, is a part of a developing class of smart drugs, designed to deliver a toxic payload directly to tumor cells. A fusion of an antibody, the drug works by recognizing a protein expressed by breast cancer cells, known as trop2, and the metabolite of an established chemotherapy drug (irinotecan), SN-38. The antibody then delivers SN-38 directly to the cancer cell.

According to BreastCancer.org, metastatic triple-negative breast cancer is an aggressive disease which does not express the estrogen receptor, progesterone receptor or HER2. Therefore, targeted therapies, such as hormone therapy or Herceptin, do not work for this type of cancer. Traditionally, treatments only included chemotherapy. It commonly affects young women and African-American women, and approximately 10% to 20% of breast cancers are triple-negative breast cancers.

This study, published in the New England Journal of Medicine, included 108 women with metastatic triple-negative breast cancer who had been through 2 or more previous treatment regimens. Oftentimes, if a patient has started her third or fourth treatment regimen, the chance of response is low.

However, with sacituzumab govitecan, patients had a better response rate than with other standard therapies. Overall, 33% of the patients responded to the drug, with the median duration of response at approximately 7.7 months. The median overall survival was 13 months, and 9 long-term responders remained free of disease progression for more than a year.

According to the study’s senior author, Kevin Kalinsky, MD, MS, the smart drug has the potential to change practice, due to overwhelming data. "There's an unmet need for patients with metastatic triple-negative breast cancer, and we see significant tumor shrinkage with this new therapy," Dr Kalinsky said. He added that sacituzumab govitecan can be delivered at a much higher dose of the payload, since it is sent directly to the cancer cells.

A randomized Phase 2/3 clinical trial comparing sacituzumab govitecan to other drugs is ongoing and the drug is currently being tested in other types of breast cancer, bladder cancer, and prostate cancer.

"We saw significant tumor shrinkage with the drug, and it took longer for the cancer to progress compared to other drugs commonly used to treat metastatic triple-negative breast cancer," Kalinsky concluded.