The Food and Drug Administration (FDA) has approved Keytruda® (pembrolizumab) for treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
The approval was based on data from the randomized, double-blind, placebo-controlled phase 3 KEYNOTE-522 trial (ClinicalTrials.gov Identifier: NCT03036488), which included 1174 patients with newly diagnosed previously untreated high-risk early-stage TNBC. Patients were randomly assigned 2:1 to receive either pembrolizumab plus chemotherapy (n=784) or placebo plus chemotherapy (n=390).
The coprimary endpoints were pathological complete response (pCR) rate, defined as the absence of invasive cancer in the breast and lymph nodes as assessed by a blinded local pathologist at the time of definitive surgery, and event-free survival (EFS), defined as the time from randomization to the first occurrence of any of the following events: progression of disease that precludes definitive surgery, local or distant recurrence, second primary malignancy, or death due to any cause.
Results showed a pCR rate of 63% (95% CI, 59.5-66.4) for the pembrolizumab plus chemotherapy arm compared with 55.6% (95% CI, 50.6-60.6) for the placebo arm (treatment difference, 7.5; 95% CI, 1.6-13.4). The proportion of patients who experienced an EFS event was 16% (n=123) in the pembrolizumab plus chemotherapy arm vs 24% (n=93) in the placebo arm (hazard ratio [HR] 0.63; 95% CI, 0.48-0.82; P =.00031). At the protocol’s prespecified interim analysis, the overall survival data was not mature with 45% of the required events for the final analysis.
“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 Dr Vicki Goodman, vice president, clinical research, Merck Research Laboratories. “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.”
The FDA also granted regular approval to Keytruda in combination with chemotherapy for patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (combined positive score [CPS] ≥10), as determined by an FDA approved test. The regular approval was granted based on confirmatory data from the KEYNOTE-522 trial. In November 2020, the FDA granted accelerated approval based on findings from the phase 3 KEYNOTE-355 trial (ClinicalTrials.gov Identifier: NCT02819518).
- 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 & Co., Inc. Accessed July 27, 2021. https://www.businesswire.com/news/home/20210727005394/en/FDA-Approves-KEYTRUDA%C2%AE-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.
- FDA approves pembrolizumab for high-risk early-stage triple-negative breast cancer. News release. US Food and Drug Administration. Accessed July 27, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pembrolizumab-high-risk-early-stage-triple-negative-breast-cancer.
- Keytruda [package insert]. Whitehouse Station, NJ: Merck & Co., Inc.; 2021.