FDA Approves Pembrolizumab for High-Risk Early-Stage Triple-Negative Breast Cancer


The combination of pembrolizumab and chemotherapy marks the first immunotherapy regimen approved for patients with high-risk early-stage triple-negative breast cancer.

Officials with the FDA have approved pembrolizumab (Keytruda, Merck) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as a neoadjuvant treatment, and then continued as a single agent after surgery.

This combination marks the first immunotherapy regimen approved for this patient population and is the 30th indication approved for pembrolizumab in the United States, according to a press release. Pembrolizumab is an anti-programmed cell death protein 1 (PD-1) therapy.

Data supporting the approval come from the phase 3 KEYNOTE-522 trial, which found that pembrolizumab in combination with chemotherapy before surgery and continued as a single agent after surgery significantly prolonged event-free survival rates in patients with previously untreated stage II or stage III TNBC.

Investigators saw a 37% reduction in the risk of disease progression that precluded definitive surgery, a local or distant recurrence, a second primary cancer, or death from any cause in the trial population. Recurrence is incredibly common among breast cancer survivors, making these findings especially significant, according to the researchers.

“Even with TNBC is diagnosed early, 30% to 40% of patients will suffer cancer recurrence after standard neoadjuvant chemotherapy and surgery,” said Joyce O’Shaughnessy, MD, chair of breast cancer research at Baylor University Medical Center, in a press release. “Therefore, there is a high unmet for new treatment options. Today’s approval is very welcome news and has the potential to change the treatment paradigm by now including an immunotherapy as part of the regimen for patients with high-risk early-stage TNBC.”

In the trial, 1174 patients were enrolled with newly diagnosed previously untreated high-risk early-stage TNBC. They were included regardless of programmed death ligand 1 (PD-L1) expression and were randomized 2:1 to receive either pembrolizumab both preoperatively with chemotherapy and as neoadjuvant monotherapy or to receive placebo with standard chemotherapy.

The main efficacy outcomes were pathological complete response (pCR) rate and event-free survival. According to the press release, patients in the pembrolizumab arm had a pCR rate of 63%, compared with 55.6% in the placebo arm. Similarly, just 16% of patients in the pembrolizumab arm experienced a recurrent event, compared with 24% in the placebo arm.

The median duration of exposure to pembrolizumab was 13.3 months and fatal adverse events (AEs) occurred in 0.9% of patients receiving pembrolizumab. Serious AEs occurred in 44% of patients in the pembrolizumab arm and serious AEs in 2% or more of patients included febrile neutropenia, pyrexia, anemia, and neutropenia. AEs leading to the interruption of pembrolizumab occurred in 57% of patients.

Immune-mediated reactions can occur during treatment with pembrolizumab and can affect any organ system or tissue and more than 1 body system simultaneously. Immune-mediated AEs include pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the US in younger women and in Black women,” said Vicki Goodman, MD, vice president of clinical research at Merck Research Laboratories, in the press release. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with Keytruda is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”


FDA approves Keytruda (pembrolizumab) for treatment of patients with high-risk early-stage triple-negative breast cancer in combination with chemotherapy as neoadjuvant treatment, then continued as single agent as adjuvant treatment after surgery. News release. Merck. July 27, 2021. Accessed July 27, 2021. https://www.merck.com/news/fda-approves-keytruda-pembrolizumab-for-treatment-of-patients-with-high-risk-early-stage-triple-negative-breast-cancer-in-combination-with-chemotherapy-as-neoadjuvant-treatment-then-continued/

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