On July 26, 2021, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda®) for high-risk, early-stage, triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment and continued as a single agent as adjuvant treatment after surgery. 

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

FDA also granted regular approval to pembrolizumab in combination with chemotherapy for locally recurrent unresectable or metastatic TNBC tumors that express PD-L1 (combined positive score ≥ 10) as determined by an FDA-approved test. FDA granted accelerated approval to pembrolizumab for the indication in November 2020. 

The trial was the basis of the neoadjuvant and adjuvant approval, as well as the confirmatory trial for the accelerated approval. 

The efficacy of pembrolizumab in combination with neoadjuvant chemotherapy followed by surgery and continued adjuvant treatment with pembrolizumab as a single agent was investigated in a randomized, multicenter, double-blind, placebo-controlled trial (KEYNOTE-522, NCT03036488) conducted in 1,174 patients with newly diagnosed, previously untreated, high-risk, early-stage TNBC (tumor size > 1 cm but ≤ 2 cm in diameter with nodal involvement, or tumor size > 2 cm in diameter regardless of nodal involvement). Patients were enrolled regardless of tumor PD-L1 expression. 

Patients were randomized 2:1 to receive either pembrolizumab in combination with chemotherapy or placebo in combination with chemotherapy. The chemotherapy regimen’s details are outlined in pembrolizumab’s drug label

The main efficacy outcome measures were pathological complete response (pCR) rate and event-free survival (EFS). The pCR rate was 63% (95% CI = 59.5, 66.4) for patients who received pembrolizumab in combination with chemotherapy compared with 56% (95% CI = 50.6, 60.6) for patients who received chemotherapy alone. The number of patients who experienced EFS was 123 (16%) and 93 (24%), respectively (HR = 0.63; 95% CI = 0.48, 0.82; p = 0.00031). 

The most common adverse reactions reported in more than 20% of patients in trials of pembrolizumab in combination with chemotherapy were fatigue or 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. 

The recommended dosage of pembrolizumab for TNBC is 200 mg every three weeks or 400 mg every six weeks via IV infusion over 30 minutes. Pembrolizumab is administered in combination with chemotherapy as neoadjuvant treatment for 24 weeks, then as a single agent for adjuvant treatment for up to 27 weeks. 

View the full prescribing information for pembrolizumab

FDA used the Real-Time Oncology Review pilot program, which streamlined data submission prior to filing of the entire clinical application, and Assessment Aid, a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application approximately five months ahead of its goal date. 

The application was granted priority review and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry—Expedited Programs for Serious Conditions—Drugs and Biologics

Healthcare professionals should report all serious adverse events they suspect are associated with the use of any medicine or device to FDA’s MedWatch Reporting System or by calling 800-FDA-1088. 

For assistance with single-patient oncology investigational new drug applications, contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov