News > Pembrolizumab approved for high-risk triple-negative breast cancer

Pembrolizumab approved for high-risk triple-negative breast cancer

FDA announces the first immunotherapy medicine approved for early-stage breast cancer


The immunotherapy can now be given with chemotherapy before surgery and continued on its own after surgery in people whose cancer is considered high risk because of a large tumor or cancer found in the lymph nodes.

The July 26 announcement comes weeks after the pharmaceutical company Merck shared new data confirming that people taking pembrolizumab in the KEYNOTE-522 trial went longer without cancer returning than people given chemotherapy with a placebo.



Triple-negative breast cancers do not express the receptors for estrogen, progesterone, or the HER2 protein, three pathways that have been successfully targeted to aid in killing cancer cells. Between 15 and 20 percent of breast cancer diagnoses in the U.S. are triple-negative, and rates are higher in Black women than in white women. Until very recently, chemotherapy has been the only effective full-body treatment for this diagnosis.

Pembrolizumab is an immunotherapy, specifically an anti-PD-1 therapy, meaning it uses the immune cells that your body employs to protect you from diseases to attack cancer cells. The PD-L1 protein in tumors stops immune cells from attacking the cancer. But when a medicine like pembrolizumab blocks PD-L1, the immune system is able to attack and kill cancer cells.

Pembrolizumab is already FDA approved to treat many types of advanced cancers, including metastatic breast cancer that tests positive for PD-L1 expression.



The FDA approval of pembrolizumab was based on findings from the phase III KEYNOTE-522 trial. The trial studied 1,174 people who had early-stage, triple-negative breast cancer with certain features that signaled a high risk of cancer returning after treatment. Cancers were considered high risk if they fell into either of two categories:

  • The breast tumor was at least 1 cm in size and cancer was found in the lymph nodes.
  • There was no cancer in the lymph nodes, but the breast tumor was at least 2 centimeters in size.

Everyone in the study received chemotherapy before surgery, along with either pembrolizumab or a placebo. After surgery, participants continued on either pembrolizumab alone or the placebo alone for a year, based on the treatment they were assigned to at the start.

The study had two primary endpoints, or measures that researchers determined before the trial started to determine whether the trial treatment worked better than standard treatment:

  • Pathological complete response rate measures how many people had no sign of cancer when they had surgery after being treated with medicine.
  • Event-free survival is how long people went, on average, without cancer returning, another cancer developing, or dying from any cause.

The study’s primary goals were to determine if the addition of pembrolizumab to standard chemotherapy improved these measures in a way that was meaningful to treatment and not the result of chance.

The first report of the study, presented at the European Society for Medical Oncology Congress in 2019, found that treatment with pembrolizumab led to higher rates of pathological complete response. But the results at that time had not yet proven a difference in event-free survival.



In July 2021, Merck announced that it had updated findings from KEYNOTE-522 that found the trial had now met both of its primary endpoints.

The updated findings showed that fewer people in the pembrolizumab group had cancer return, progress, or develop after being assigned to treatment. After being followed for 3 years:

  • 84.5 percent of people given pembrolizumab had no cancer event
  • 76.8 percent of people in the placebo group had no cancer event

The findings were statistically significant, meaning they were not likely the result of chance.

The update showed also that people given pembrolizumab were still more likely to have a pathological complete response — meaning there was no remaining cancer found when they had surgery. At the time of surgery:

  • 63 percent of people given pembrolizumab had no sign of cancer.
  • 55.6 percent of people in the placebo group had no sign of cancer.

Researchers reported that side effects were what they had expected based on earlier studies, and the most common ones were driven by chemotherapy. Some notable side effects in the pembrolizumab group required medical attention, including febrile neutropenia, a condition that includes fever and very low levels of white blood cells that are needed to fight infections that was seen in 15 percent of people given pembrolizumab. They also reported fevers from other causes in 37 percent of the group.

Treatment was stopped in 20 percent of people, the most common reasons were rashes and high levels of certain enzymes in the liver.

Based on these updated results, the FDA approved pembrolizumab for use in early-stage, triple-negative breast cancer on July 26.


What this means for you

People with triple-negative breast cancer have not benefitted from the same advances in targeted therapy that have changed treatment in other breast cancer subtypes. The approval of pembrolizumab marks an important step toward more effective treatment for this diagnosis.

“Even when diagnosed early and treated aggressively, one-third of patients diagnosed with triple-negative breast cancer experience a recurrence,” says Rita Nanda, MD, associate professor of medicine and director of the breast oncology program at The University of Chicago.


The approval of pembrolizumab for high-risk, early-stage, triple-negative breast cancer is a big step forward in improving outcomes for those diagnosed with this aggressive form of breast cancer. The findings from the KEYNOTE-522 trial are exciting and practice changing.”

Rita Nanda, MD


It’s important to remember that pembrolizumab is not for everyone with triple-negative breast cancer. This study looked at some very specific groups of people and described what it means to be at higher risk. If there is a low chance of cancer returning, based on the size and extent of the cancer, adding pembrolizumab has not been shown to affect your risk for recurrence. It’s OK to ask your healthcare team to explain why they do or do not recommend a treatment for you.


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