Keytruda (pembrolizumab) received FDA approval for high-risk, early-stage, triple-negative breast cancer in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
Keytruda is sponsored by Merck.
FDA also granted regular approval to pembrolizumab 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.
FDA granted accelerated approval to pembrolizumab for this indication in November 2020.
The following 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 KEYNOTE-522 (NCT03036488), a randomized, multicenter, double-blind, placebo-controlled trial conducted in 1174 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 pembrolizumab in combination with chemotherapy or placebo in combination with chemotherapy. Details of the chemotherapy regimen are in the drug label linked below.
The main efficacy outcome measures were pathological complete response rate and event free survival. 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 an EFS event was 123 (16%) and 93 (24%), respectively (HR 0.63; 95% CI: 0.48, 0.82; p=0.00031).
