News > Pembrolizumab benefits common across subgroups in early-stage, triple-negative breast cancer

Pembrolizumab benefits common across subgroups in early-stage, triple-negative breast cancer

Updates from a recent study show improvements in pathological complete response affect women with different personal and tumor features


Update: Pembrolizumab (Keytruda) was FDA approved for early-stage, high-risk triple-negative breast cancer in July 2021. This article explains the research that supported the FDA approval. Learn more about pembrolizumab (Keytruda).


A new study released this fall, Keynote-522, showed that pembrolizumab (Keytruda) added to neoadjuvant chemotherapy for early-stage, triple-negative breast cancer led to higher rates of pathological complete response at the time of surgery. Additional results presented at the San Antonio Breast Cancer Symposium (SABCS) on Thursday provide a closer look at how pembrolizumab affected subgroups within the trial cohort.


PD-L1 is a protein that plays a role in telling the immune system whether a cell is part of your body or is a disease. PD-L1 checkpoint inhibitors, like pembrolizumab, block the interaction with cancer cells that let them pass as part of your body. Your immune system can then treat the cancer cells as disease and destroy them.

Pembrolizumab is currently approved to treat tumors with specific features across a number of different cancer types, including metastatic breast cancer.

The Keynote-522 study explored using pembrolizumab to treat early-stage, triple-negative breast cancer. It was tested in neoadjuvant therapy, meaning that it was given before surgery to remove the tumor. All participants were given standard chemotherapy, and they were randomized to get either pembrolizumab or a placebo along with the chemotherapy. After surgery, participants continued to receive pembrolizumab or the placebo (whichever they were assigned at randomization) for an additional 27 weeks without chemotherapy.

The primary endpoints for the trial were pathological complete response at the time of surgery and event-free survival. Pathological complete response means that there is no sign of cancer in the breast. Studies have shown that people who get a pathological complete response are less likely to have cancer return. Event-free survival is how long people go without cancer returning or traveling to other parts of the body.


As we learned earlier this fall, Keynote-522 found that people given pembrolizumab were more likely to have a pathological complete response than people in the placebo group:

  • 64.8 percent of people in the pembrolizumab group showed a complete response.
  • 51.2 percent of people in the placebo group showed a complete response.

Researchers also reported that pembrolizumab appears to be associated with higher event-free survival at 18 months, but that data is not yet statistically significant, meaning the results are not strong enough to say they are not a product of chance. Follow-up studies will provide more answers on event-free survival.

At SABCS, lead investigator Peter Schmid, MD, shared more information about subgroups within the trial to see if the effect of pembrolizumab on complete response rates was common or if it was more effective in cancers with certain features than others.

The study found that pembrolizumab resulted in higher complete response rates in almost every category reported, including cancers that tested negative for PD-L1 expression, cancers that tested positive for PD-L1, and cancers that did not get the full chemotherapy dose recommended in the trial.

The groups that saw the greatest benefit from adding pembrolizumab to treatment were those with breast cancer that traveled to the lymph nodes and people with higher stages of breast cancer. Complete response rates did improve for people with lower stage cancers and no cancer in the lymph nodes, but the difference in complete response rates between those given pembrolizumab and those given placebo was greater for people in these groups:

  • For people with no cancer in their lymph nodes, the rate of pathological complete response was 6.3 percentage points higher for the pembrolizumab group than for the placebo group.
  • For people with cancer found in their lymph nodes, the rate of pathological complete response was 20.6 percentage points higher than the placebo group.

What this means for you

The trend in treatment research is giving appropriate medicines to people who need them without giving anyone unnecessary treatments. The Keynote-522 trial created a lot of excitement this fall with results that suggest it may come into use in early-stage, triple-negative breast cancer. But, as Kevin Kalinsky, MD, MS, of NewYork-Presbyterian Hospital/Columbia University Medical Center mentioned in a discussion at SABCS Thursday morning, it is another treatment given to people already given four different chemotherapy medicines. Looking at subgroups helps identify if there are people who really should be getting this medicine, and if there are groups who may not be benefitting from adding another medicine to their treatment.

Thursday’s presentation reinforced the exciting results from earlier this season, showing benefits for every group identified in this study of people with early-stage, triple-negative breast cancer. It further showed that groups with the highest expected risk of recurrence were the ones that had the greatest change in pathological complete response.

Two things yet to be seen are FDA approval and event-free survival data showing that pembrolizumab has resulted in fewer people having cancer return.


We caught up with Peter Schmid, MD, the lead investigator for this study.


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