Sacituzumab govitecan shows promise for metastatic triple-negative breast cancer

Update: Sacituzumab govitecan received accelerated FDA approval in April 2021. This article helps you understand some of the research that supported the FDA approval of Trodelvy.

A study published in the New England Journal of Medicine showed positive results for people with metastatic triple-negative breast cancer taking sacituzumab govitecan. In the phase I/II trial, 108 people who had at least two previous treatments were given sacituzumab govitecan.

Background

Triple-negative breast cancers don’t respond to the hormones estrogen or progesterone and don’t express the protein HER2. While various targeted therapies are available for other breast cancer types, there are very few available for triple-negative breast cancer.

Chemotherapy remains the most effective treatment for most triple-negative breast cancers. When the cancer grows while taking one chemotherapy medicine, that chemotherapy is replaced by another.

Sacituzumab govitecan is an antibody-drug conjugate. Antibody-drug conjugates have three components:

• The targeted antibody attaches to a specific protein in breast cancer cell.
• The linker keeps the compound safe in the blood stream as it looks for the target.
• The chemotherapy kills the breast cancer cells.

By delivering the chemo in this targeted way, there is less harm to your healthy cells.

The Food and Drug Administration (FDA) named sacituzumab govitecan a breakthrough therapy for triple-negative breast cancer in 2016, which means the FDA provides extra resources for the researchers and reviews applications for this medicine more quickly than it normally would. Breakthrough therapy designation often means the medicine can make it available to the people who need it, faster.

Design

This is a phase I/II, open-label trial. There was no comparison group taking standard therapy in this study. Everyone knew that they were taking sacituzumab govitecan.

The study included 108 people with metastatic triple-negative breast cancer. All participants had at least two treatments for metastatic breast cancer in the past, and stopped getting them because the cancer grew or because of severe side effects.

During the study, sacituzumab govitecan was given by vein, with two infusions every 21-day cycle. Participants continued getting it until the cancer grew or side effects became too severe. The participants had a CT scan and an MRI before starting sacituzumab govitecan, and every 8 weeks during treatment, to measure the medicine’s effect. If the cancer appeared to shrink or disappear, additional scans were done after at least 4 weeks to confirm the finding.

Researchers’ main interest was the objective response rate — the rate of people whose cancer shrank or disappeared after beginning treatment. They also considered how:

• long it took for the response to take effect
• long the response lasted
• many people had cancers that responded or stopped growing for at least 6 months
• long people went before cancer started growing again
• long people lived after they started treatment

Results

In this study, one-third of the cancers shrank or disappeared with sacituzumab govitecan, and the median length of that response was 7.7 months. Researchers also found that people stayed on sacituzumab govitecan longer than they had their most recent previous treatment:

• Participants had been given the previous treatment for an average of 2.5 months.
• Sacituzumab govitecan was given for 5.1 months.

The most notable side effects were low blood cell counts and diarrhea. Diarrhea was reported by 62% of people in the study, and 8% had severe diarrhea that required medical care. But only three people stopped treatment with sacituzumab govitecan because of side effects.

Four participants died during the course of the study, but investigators found that the deaths were caused by the growth of breast cancer and not related to the safety of sacituzumab govitecan.

What this means for you

Most approvals usually require a larger, phase III study that compares the medicine to the current standard treatment, but sacituzumab govitecan was named a breakthrough therapy to move it along more quickly. People with metastatic triple-negative breast cancer who have already had multiple courses of treatment currently have very few targeted treatment options. Researchers then began recruiting for the phase III ASCENT trial to compare sacituzumab govitecan to standard chemotherapy treatment.

If you are interested in helping study new medicines, with the possibility of receiving them yourself, you can ask your doctor about participating in clinical trials that may be available for you.

Bardia, A, Mayer, IA, Vahdat, LT, et al. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. New England Journal of Medicine. 2019; 380 (741-751) DOI: 10.1056/NEJMoa1814213