Checkpoint inhibitor drugs have been FDA approved to treat over 10 different cancers, and they’re oftentimes very successful. One cancer in particular that they’ve shown a lot of potential is in triple-negative breast cancer, an aggressive form of the disease that is notoriously difficult to treat.
Data from preliminary studies showed that first-line response rates were around 20-26%, but later-line response rates, after women had been treated with chemotherapy, were not promising. However, when researchers used pembrolizumab on women who had not yet had surgery, and combined it with chemotherapy treatments, they saw much different results. The combination greatly improved the patient response rate. These results suggested to researchers that using the checkpoint inhibitors early on in the treatment process could make a big difference.
Current research is working to try and change PD-L1-negative breast cancers that are either metastatic or have been pretreated so that the cells become more vulnerable to immunotherapy treatments. One trial is combining the HDAC (histone deacetylase) inhibitor entinostat with the checkpoint inhibitor atezolizumab. Using the inhibitor can increase neoantigens and DNA repair deficiency, which could make cancer more susceptible to be destroyed by immune checkpoint inhibitors. This is just one of many strategies currently being investigated in this area.
Overall, researchers have found that the combination of checkpoint inhibitors with chemotherapy is producing better results in patients with other cancers. Scientists have studied this phenomenon in metastatic triple-negative breast cancer patients as well. Placing nab-paclitaxel with atezolizumab showed positive response rates, close to 50% in a first-line setting, which is much higher than studies with nab-paclitaxel alone. Researchers believe that the combination of the two therapies could alter the microenvironment of the breast cancer, possibly even decreasing T-regulatory cells. Teams are still studying the exact effects that chemotherapy can have on the microenvironment, but so far, they know that it can prime cancer for destruction via immune checkpoint inhibitors.