In both studies, pembrolizumab, used in combination with chemotherapy, proved effective at delaying TNBC growth or spread. It is recommended as a standard treatment for both high-risk, early-stage, and certain metastatic triple-negative breast cancers.
Few treatment options exist for people with triple-negative breast cancer. As new treatments emerge for other types of breast cancer, doctors continue to rely primarily on chemotherapy for TNBC.
Pembrolizumab belongs to a group of immunotherapy drugs called checkpoint inhibitors. It was first approved by the U.S. Food and Drug Administration (FDA) to treat lung cancer in 2016. It is now used in many other cancers including skin, bladder, and GI. Pembrolizumab works by blocking the PD-1 protein. In cancer, this protein can bind with PD-L1 to interfere with immune response.
Doctors often test the PD-L1 level of the cancer before trying pembrolizumab. A higher level can mean that the drug is more likely to work. With some cancers, the drug can be effective regardless of PD-L1 level. In others, it is only used when the PD-L1 level is at least a certain number. The cut-off number can vary.
Prior studies established that pembrolizumab was safe and worked against metastatic triple-negative breast cancer, especially when used as the first-line treatment. Studies in early-stage disease suggested that pembrolizumab could be given before surgery, as a neoadjuvant , or initial, therapy.
This update focuses on KEYNOTE 522 and KEYNOTE 355. KEYNOTE 522 is a randomized phase III trial of pembrolizumab for high-risk, early-stage TNBC. It is the first trial of this kind to test immunotherapy for early-stage TNBC both before and after surgery. KEYNOTE 355 is a randomized trial of pembrolizumab in people with metastatic TNBC.
The KEYNOTE 522 trial included 1,174 people with stage II or stage III triple-negative breast cancer. Participants were randomly assigned to two groups. The first group, which included two-thirds of participants, received pembrolizumab along with chemotherapy. The second group received the same chemo drugs and a placebo. Participants started the combination treatment before surgery. They completed eight cycles of treatment over 24 weeks. After surgery, they continued treatment, this time with pembrolizumab or placebo only. Treatment lasted for up to nine cycles over 27 weeks. The most common side effects were nausea, hair loss, and anemia.
The trial looked at both pathological response, measured in the lab, and event-free survival (EFS) as noted by doctors. The average length of time on trial was 39 months. The results were analyzed by subgroup and as a whole. In all cases, the participants treated with pembrolizumab did better than those without. It increased EFS to 84.5 percent, up from 76.8 percentt. The drug was effective for premenopausal and postmenopausal women, with different sized tumors, with and without cancer in the lymph nodes.
In people with metastatic TNBC, researchers found that PD-L1 level counts. In KEYNOTE 355, final results show the drug works best for people with a PD-L1 level of 10 or higher. Within this group, 38 percent saw a benefit from pembrolizumab.
This finding is based on a study of 847 people with metastatic TNBC. The average age of participants was 53. The group included people with de novo disease and people whose cancer had returned. The most common side effects were hypo- or hyperthyroidism, and hair/skin effects including discoloration.
What it means for people with TNBC
Pembrolizumab is now a treatment option for many people with TNBC. It is recommended as a first treatment for people with high-risk early stage TNBC. Patients can receive the drug with chemotherapy before surgery then on its own after surgery.
Pembrolizumab plus chemotherapy is a standard treatment for people with metastatic TNBC who have PD-L1 levels of 10 or higher. This is a change from a year ago when the FDA first granted accelerated approval for pembrolizumab as a treatment for metastatic TNBC. At that time, it was an option for people with a PD-L1 level over 1. The new trial results show that only those with levels over 10 may benefit from the drug.
The update means that patients with metastatic disease may need to have PD-L1 testing before starting the drug. This could be a barrier for people who receive care at a cancer center or health center that does not offer this testing.
There are still unanswered questions. Why does the PD-L1 level only matter for metastatic disease? How long should people with early-stage disease stay on pembrolizumab if they are tolerating it well? As researchers continue to analyze the data, we also may learn more about how the drug worked for different TNBC molecular subtypes.