A promising new agent in the treatment of the most aggressive type of breast cancer
Global Clinical Study Confirms Efficacy of Targeted Antibody Drug Combination Against Metastatic Triple-Negative Breast Cancer Refractory to Other Treatment
In a global phase 3 clinical study It has been discovered that a single antibody drug conjugate (ADC), that delivers a high dose of a drug to tumor cells through a targeted antibody. Study showed it nearly doubled the survival time of patients with refractory, metastatic triple-negative breast cancer. The study of the ADC drug sacituzumab govitecan (SG), for which Massachusetts General Hospital (MGH) was a lead clinical research center after serving as the primary site for the pivotal phase 1/2 trial, reported superior results compared with single-agent chemotherapy, the standard for the treatment of metastatic triple-negative breast cancer. Results from the phase 3 study, known as ASCENT, were published in the New England Journal of Medicine.
“Favorable results were seen with SG versus chemotherapy in terms of progression-free survival (the amount of time between the start of treatment and the progression of the cancer); and overall survival (the length of time before death from any cause), says global principal investigator Aditya Bardia, MD, MPH, an attending physician in the Department of Medical Oncology at the Mass General Cancer Center. “These statistically significant findings give patients with this serious disease new hope. We need to build on that progress and accelerate the development of antibody drug conjugates and combination therapies for breast cancer patients.”
Metastatic triple negative breast cancer is the most aggressive type of breast cancer with a poor prognosis. Chemotherapy remains the only standard treatment option, but it is associated with low response rates and short progression-free survival. SG, which was developed and manufactured by Immunomedics, a subsidiary of Gilead Sciences, has received accelerated approval from the US Food and Drug Administration. in April 2020 based on favorable phase 1/2 clinical trials, with full approval contingent on phase 3 confirmation of results.
ASCENT is a global study to evaluate the safety and efficacy of antibody-drug conjugate compared to chemotherapy in 529 patients with triple-negative metastatic breast cancer whose cancer had relapsed or was resistant to at least two other types of therapy. The researchers found that median progression-free survival with the ADC agent was 5.6 months compared to 1.7 months with chemotherapy, and median overall survival was 12.1 months with the ADC agent compared with 6.7 months with chemotherapy. The study also found that the response rate, that is, the reduction in the size of metastatic tumor sites, was 35% after administration of ADCs compared to 5% with chemotherapy.
ADCs are complex molecules that combine the targeting ability of monoclonal antibodies with the cancer-killing potency of cytotoxic drugs. In the case of sacituzumab govitecan, the monoclonal antibody seeks out the antigen (or protein), known as Trop-2, that is overexpressed on the surface of tumor cells, and delivers the anticancer drug SN-38 in a highly concentrated dose that kills cancer cells without affecting normal cells. ADCs have been established as a treatment option for HER2-positive breast cancer.
“We believe that antibody-drug conjugates hold particular promise as building blocks for effective new combination treatments,” says Bardia. “The goal is not only to improve patient outcomes, but also to establish ADCs as first-line therapy or even earlier, so that these powerful agents can play a role in preventing the spread of triple-negative breast cancer.”