Positive early results for pembrolizumab in early-stage triple-negative breast cancer

Immunotherapy led to significant increase in pathological complete responses when paired with chemotherapy before surgery
Breast Cancer News
October 30, 2019
Eric Fitzsimmons
Reviewed By: 
Sara M. Tolaney, MD, MPH

Adding the immune checkpoint inhibitor pembrolizumab (Keytruda) to pre-surgeryinfo-icon chemotherapyinfo-icon led to more cases where no cancer cells were found after surgery in people with early-stageinfo-icon, triple-negative breast cancerinfo-icon. These findings come from interim results of the KEYNOTE-522 trial presented at the European Society for Medical Oncologyinfo-icon Congress in late September. If approved, this would be the first medicineinfo-icon for early-stage, triple-negative breast cancer that isn’t chemotherapy.


A triple-negative breast cancer diagnosisinfo-icon means the cancer has neither hormoneinfo-icon receptors nor HER2 receptors, pathways that targeted medicines use to kill cancer cells. Researchers have not yet found targeted therapies that work against early-stage, triple-negative breast cancer. Chemotherapy is the most effective systemicinfo-icon treatment for people with this diagnosis.

Pembrolizumab is an anti-PD-1 immunotherapy, meaning it uses the body’s immune systeminfo-icon to kill cancer cells. Cancer cells are able to signal to immune cells that they are part of your body, so that the immune cellinfo-icon won’t attack them. One of the ways they do this is expressing the PD-L1 proteininfo-icon which can bind to the PD-1 protein on the immune cell. Anti-PD-1 medicines such as pembrolizumab target the PD-1 protein, keeping cancer cells from binding to it, and freeing the immune cell to kill the cancer.

Pembrolizumab is currently approved by the Food and Drug Administrationinfo-icon to treat metastaticinfo-icon cancers, including breast cancer, with a solid tumorinfo-icon that is microsatellite instability-high or mismatch repair deficient, which is determined by testing tumorinfo-icon tissueinfo-icon.


The phase III KEYNOTE-522 trial tested pembrolizumab in early-stage, triple-negative breast cancer. People in the study were given neoadjuvant chemotherapy, chemotherapy given before breast surgery, with either pembrolizumab or a placeboinfo-icon. After breast surgery, participants continued on pembrolizumab or placebo, whichever they had been on before surgery, for another 6 months.

The trial was randomized and double blind, meaning neither the participants nor their doctors knew which participants were given pembrolizumab or a placebo.

KEYNOTE-522 has two primary endpoints: event-free survival and pathological complete responseinfo-icon. Event-free survival will compare the number of recurrences in the pembrolizumab arm and the placebo arm, but it is too early in the study for those results to be mature. Pathological complete response is when there are no remaining cancer cells after breast surgery. The results in this interim analysis focus on pathological complete response.

Pathological complete response is not a goal in itself, but is associated with lower rates of recurrenceinfo-icon. The FDAinfo-icon often uses measures such as pCR as a “surrogate endpointinfo-icon,” a sign that a medicine is working before getting all the final data, for accelerated approval and other programs to make potentially life-saving medicines available faster.


Of 602 participants in this analysis, those taking pembrolizumab were more likely to have pCR at surgery than people who were given a placebo:

  • 64.8 percent of people given pembrolizumab had a pCR.
  • 51.2 percent of people given a placebo had a pCR.

These results were statistically significantinfo-icon, meaning they likely aren’t a result of chance, and the 13.6-percentage-point difference in pCR rates seems very promising for patients with early stage triple-negative breast cancer.

“Now 60 or nearly 65 percent pCR rates, which are the highest pCR rates we've ever seen in early triple-negative breast cancer in a neoadjuvant study, and knowing that pCR is linked with long-term outcomes, makes me hugely optimistic that we hopefully cureinfo-icon more patients,” Peter Schmid, MD, PhD, said in a conversation with LBBC. Dr. Schmid is the chair of cancer medicine at Barts Cancer Institute, Queen Mary University London, and lead investigatorinfo-icon of the trial.

Researchers did present early results for event-free survival that show more people going without cancer returning, but this was not statistically significant. It will take more time for researchers to present conclusive data on that endpoint.

The side effects were what researchers expected, according to Dr. Schmid. Most were driven by the chemotherapy that is given with pembrolizumab, and additional side effects were in line with what is already known about pembrolizumab, including known immune-related side effects.

What this means for you

The possibility of a new treatment is always exciting, and is especially rare in early-stage, triple-negative breast cancer. Dr. Shmid says, if the FDA approves this medicine and the benefit of this treatment is reflected in the event free survival results, this could be the first non-chemotherapy medicine for routine use in this diagnosis.

“I think this trial, the KEYNOTE-522 trial, has the potential to be a practice-changing trial and it's probably, for many, already a practice-changing trial,” Dr. Schmid says.

These are early results and it will be very important to watch for the future findings. Pembrolizumab is given alongside chemotherapy, which will continue to be a key part of early-stage, triple-negative breast cancer treatment. The pCR findings are enough that it is likely to get consideration from the FDA soon, in the hopes of making a helpful medicine available to people sooner. It’s possible the agency may wait to see event-free survival results.

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