Tremelimumab (tentative Chinese name trimethoprim) is a cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor, similar to the big-name PD-1/PD-L1 inhibitors, which are also immunotherapy drugs. The drug is in the investigational phase and is not available.
Tremelimumab for breast cancer is still being explored, and this article takes a look at this iconic immunotherapy drug.
Mechanism of action: immune checkpoint blockade
Tremelimumab, unlike traditional targeted therapies, does not kill tumor cells directly, but acts indirectly by modulating the body’s immune system.
The cytotoxic T lymphocyte (CTL) is an immune cell in the body that has the ability to recognize and kill cancer cells, but its ability to do so is interrupted by a “switch” (called an immune checkpoint) that prevents it from killing cancer cells.
The CTLA-4 is one of the immune checkpoint “switches”.
By “turning off” the inhibitory effect of CTLA-4 on immune cells, Tremelimumab can fully engage CTL to keep killing cancer cells, a process also known as immune checkpoint “blockade”.
Triple-negative breast cancer may be sensitive to Tremelimumab treatment
There are not many clinical studies of Tremelimumab for breast cancer, and it is in a relatively early stage.
A phase I clinical study enrolled 26 patients with recurrent advanced postmenopausal breast cancer, 25 of whom were hormone receptor-positive. Patients in the study tolerated Tremelimumab in combination with exemestane well, and most adverse events were mild to moderate, but outcomes were poor: 42% of patients had relatively stable disease at 3 months, although tumors did not shrink significantly.
A small study reported in 2018 offers a glimmer of hope for Tremelimumab for breast cancer. 11 hormone receptor-positive advanced breast cancers and 8 triple-negative advanced breast cancers were treated with Tremelimumab in combination with Durvalumab (PD-L1 inhibitor).
The overall response rate for patients was only 15%, but the remission rate for patients with triple-negative breast cancer was 43%. Such numbers are not very convincing, and one can only infer that patients with advanced triple-negative breast cancer appear to be more sensitive to a combination immunotherapy regimen that includes Tremelimumab.
Summary
Tremelimumab has been the first to show some therapeutic potential in metastatic triple-negative breast cancer, but it is too early to draw premature conclusions.
Investigators are still actively trying to find people with breast cancer suitable for Tremelimumab treatment, and studies are ongoing, such as in HER2-negative brain metastases and inoperable locally recurrent or metastatic breast cancer, among others.