FDA Approves Pembrolizumab for High-Risk Early-Stage TNBC


The FDA has approved the first immunotherapy, pembrolizumab (Keytruda), to treat patients with high-risk early-stage triple-negative breast cancer.

The FDA approved pembrolizumab (Keytruda) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, to be continued as an adjuvant monotherapy after surgery.

The approval was based off findings from the randomized, multicenter, double-blind, placebo-controlled KEYNOTE-522 trial (NCT03036488). Data from this study indicated that the use of pembrolizumab as a neoadjuvant therapy with chemotherapy significantly increased the pathologic clinical response. The findings showed a 37% reduction in the risk of disease progression that precluded definitive surgery, a local/distant recurrence, a second primary cancer, or death from any cause (HR, 0.63; 95% CI, 0.48-0.82; P = .00031).

In addition, adjuvant pembrolizumab following surgery displayed a favorable trend in event-free survival (EFS): 16% vs 24%, respectively (HR, 0.63; 95% CI, 0.48-0.82).

The study reported that adverse events (AEs) were consistent with the preexisting safety profiles of each agent. The median duration of exposure to pembrolizumab was 13.3 months. Fatal reactions from pembrolizumab treatment occurred in 0.9 % of patients. Serious AEs occurred in a little less than half (44%) of patients and included febrile neutropenia, pyrexia, anemia, and neutropenia. The most common AEs resulting in the permanent discontinuation of pembrolizumab were increased alanine aminotransferase, increased aspartate aminotransferase, and rash.

“Even when 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, Baylor University Medical Center, Texas Oncology, U.S. Oncology, Dallas, Texas, in a press release. “Therefore, there is a high unmet need 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.”

The study evaluated patients who were previously untreated, non-metastatic, and had been diagnosed with centrally confirmed TNBC. Participants were randomized 2:1 to receive either 200 mg of pembrolizumab or preoperative placebo paired with 4 cycles of carboplatin and paclitaxel, continued with 4 cycles of doxorubicin or epirubicin and cyclophosphamide. Following surgery, the 2 groups were then treated with either pembrolizumab or placebo as a monotherapy for either 9 cycles or until unacceptable toxicity was reached. Patients were separated by nodal status, tumor size, and carboplatin schedule.

End points included pathologic complete response and EFS. pCR was defined as an absence of invasive cancer in the breast and lymphs (ypT0/Tis or ypNO) while EFS was measured from the time of randomization to the first occurrence of disease progression. Secondary end points included partial complete response where pCR was defined as ypT0 ypN0 and ypT0/Tis, overall survival and efficacy in the pD-L1 L1þ population.

The age of participants ranged from 22 to 80 years and the mean age was 49. Ninety-nine percent of the participants were female, and 64% were white.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the U.S. in younger women and in Black women,” expressed Vicki Goodman, MD, vice president, clinical research, Merck Research Laboratories, in a 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.”


This KEYTRUDA combination is the first immunotherapy regimen approved for high-risk early-stage triple-negative breast cancer (TNBC). 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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