News > Pembrolizumab before surgery shows benefit in ER+ breast cancer | SABCS 2023

Pembrolizumab before surgery shows benefit in ER+ breast cancer | SABCS 2023

Immunotherapy/chemotherapy combination kills cancer cells before surgery in early-stage, ER+/HER2- breast cancer

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The immunotherapy pembrolizumab first gained FDA approval for use in lung cancer in 2016. Since then, it has been proven effective against many different cancer types and stages and is currently part of the standard of care for early-stage and metastatic triple-negative breast cancer (TNBC).

Pembrolizumab blocks an immune cell protein called PD-1 from interacting with a protein present on some breast cancer cells, called PD-L1. Blocking this interaction enables the immune system to destroy cancer cells. In metastatic TNBC, eligibility to take pembrolizumab requires that the cancer test positive for a certain level of the PD-L1 protein. Still, for reasons that are not entirely known, pembrolizumab sometimes works against cancer even when PD-L1 levels are low.

For early-stage, estrogen receptor-positive, HER2-negative breast cancer, there are many effective treatment options available. While treatment once routinely began with surgery, doctors now know that some people benefit from drug therapy before surgery. This approach — called neoadjuvant therapy — can help ensure that treatment is successful and reduce the risk of cancer from returning after treatment. Neoadjuvant therapy is often used when the cancer is determined to have a high risk for recurrence.


The KEYNOTE-756 randomized control trial found that adding pembrolizumab to chemotherapy before surgery worked better than chemotherapy alone in people with stage II or stage III estrogen receptor-positive, HER2-negative breast cancer. The randomized trial divided participants into two groups. Half received pembrolizumab plus chemotherapy and the other half placebo plus chemotherapy.

The study looked at pathological complete response (pCR). Pathological response measures the presence of invasive cancer cells after neoadjuvant therapy. Once neoadjuvant therapy is complete, surgeons remove breast and/or lymph node tissue to examine it for any remaining cancer cells. A pCR means that no cancer was found, and that the neoadjuvant therapy was successful.

The international study included 1,278 participants — 21% from Eastern Europe, 14% from China, and the remaining 65% from other countries. Participants were relatively young with an average age of 49. The authors found that:

  • People receiving pembrolizumab were more likely to have a pCR prior to surgery (24.3% versus 15.6%). This result was true for stage II and stage III cancers, with or without node involvement.
  • Cancers with positive lymph nodes saw greater absolute benefit than node-negative cancers.
  • Although study eligibility did not require the cancer to have a certain PD-L1 level, people with higher levels of PD-L1 had stronger responses.
  • Following chemotherapy doses as planned resulted in stronger responses, as opposed to changing the planned dose (likely due to side effects).
  • While all groups benefited, results were more robust for participants from Eastern Europe and other countries, and less so for people from China. No explanation was provided for this finding.

Pembrolizumab was well tolerated, as it has been when combined with chemotherapy for other diagnoses. Thyroid problems were the most common new side effect. No side effects led to death.

The results presented here focused on the impact of immunotherapy before surgery. This clinical trial is ongoing. Participants who remain in the trial will continue with pembrolizumab or placebo along with endocrine therapy following surgery. Some people may have radiation therapy as well. It is too early to report on the length of time before cancer return, the trial’s other key outcome.

What does this mean for you?

If you are newly diagnosed with early-stage estrogen receptor-positive, HER2-negative breast cancer, talk with your doctor about this study before you start treatment to see if you might benefit from pembrolizumab before surgery. Your doctor may want to test the cancer for its PD-L1 level. In this study, pembrolizumab was effective regardless of PD-L1 level, but participants with higher levels saw greater response.

This discussion of pembrolizumab did not focus on side effects, although the drug is generally very safe. If you are considering pembrolizumab or any new treatment, talk with your doctor about the potential additional side effects.


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