On July 26, 2021, pembrolizumab was approved for high-risk, early-stage, triple-negative breast cancer in combination with chemotherapy as neoadjuvant treatment and continued as adjuvant treatment.1
Pembrolizumab was also granted regular approval in combination with chemotherapy for locally recurrent unresectable or metastatic triple-negative breast cancer expressing PD-L1 (Combined Positive Score [CPS] ≥ 10), as determined by an U.S. Food and Drug Administration–approved test based on confirmatory data from the KEYNOTE-522 study.
Supporting Efficacy Data
Approvals were based on findings in the KEYNOTE-522 trial (ClinicalTrials.gov identifier NCT03036488), in which 1,174 newly diagnosed patients without regard to tumor PD-L1 expression were randomly assigned 2:1 to receive eight cycles of neoadjuvant pembrolizumab (n = 784) or placebo (n = 390) plus chemotherapy, followed by nine cycles of adjuvant pembrolizumab or placebo. Neoadjuvant chemotherapy consisted of four cycles of carboplatin/paclitaxel, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide.
Pathologic complete response rates were 63% (95% confidence interval = 59.5%–66.4%) in the pembrolizumab group vs 56% (95% CI = 50.6%–60.6%) in the chemotherapy group (difference = 7.5%, 95% CI = 1.6%–13.4%). Event-free survival events occurred in 16% vs 24% of patients (hazard ratio [HR] = 0.63, 95% CI = 0.48–0.82, P = .00031).
How It Is Used
The recommended dosage of pembrolizumab for high-risk early-stage triple-negative breast cancer is 200 mg every 3 weeks or 400 mg every 6 weeks, given in combination with chemotherapy for neoadjuvant treatment for 24 weeks and then as adjuvant treatment for up to 27 weeks. No dose reductions of pembrolizumab are recommended. Prescribing information provides instructions on dosage modifications for immune-mediated adverse reactions and infusion-related reactions.
The most common adverse events of any grade reported in at least 20% of patients in trials of pembrolizumab in combination with chemotherapy have been fatigue/asthenia, nausea, constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, alopecia, peripheral neuropathy, mucosal inflammation, stomatitis, headache, weight loss, abdominal pain, arthralgia, myalgia, and insomnia.
Pembrolizumab has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.
1. Keytruda (pembrolizumab) injection for intravenous use prescribing information, Merck & Co, Inc, July 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125514s089s114lbl.pdf. Accessed August 3, 2021.