The FDA has granted accelerated approval to pembrolizumab (Keytruda) in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score [CPS] ≥10) as determined by an FDA approved test.
The FDA has granted accelerated approval to pembrolizumab (Keytruda) in combination with chemotherapy for the treatment of patients with locally recurrent unresectable or metastatic triple-negative breast cancer (TNBC) whose tumors express PD-L1 (combined positive score [CPS] ≥10) as determined by an FDA approved test.1
The FDA approval was based on data from the multicenter, double-blind, randomized, placebo-controlled, phase 3 KEYNOTE-355 trial (NCT02819518), which evaluated patients with locally recurrent unresectable or metastatic TNBC who had not been previously treated with chemotherapy in the metastatic setting.
Patients were randomized 2:1 to receive 200 mg of pembrolizumab or placebo on day 1 every 3 weeks in combination with different chemotherapy treatments (paclitaxel protein-bound, or paclitaxel, or gemcitabine plus carboplatin) via intravenous infusion. The primary end point for the study was progression-free survival (PFS) as assessed by blinded independent review according to RECIST 1.1, tested in the subgroup of patients with CPS of 10 or higher.
The median PFS was 9.7 months (95% CI, 7.6-11.3) in the pembrolizumab plus chemotherapy arm and 5.6 months (95% CI, 5.3-7.5) in the placebo plus chemotherapy arm (HR, 0.65; 95% CI, 0.49-0.86; 1-sided P = .0012).
Regarding safety, the most common adverse events observed in patients
receiving pembrolizumab plus chemotherapy in KEYNOTE-355 (≥20% of patients) were fatigue, nausea, diarrhea, constipation, vomiting, alopecia, rash, cough, decreased appetite, and headache. Further, the most common laboratory abnormalities in patients receiving pembrolizumab plus chemotherapy (incidence ≥20%) were anemia, leukopenia, neutropenia, lymphopenia, thrombocytopenia, elevated liver enzymes, hyperglycemia, hypoalbuminemia, increased alkaline phosphatase, hypocalcemia, hyponatremia, hypophosphatemia,
The FDA recommended dose of pembrolizumab for adult patients with locally recurrent unresectable or metastatic TNBC is 200 mg every 3 weeks or 400 mg every 6 weeks administered prior to chemotherapy until disease progression, unacceptable toxicity, or up to 24 months. When given with pembrolizumab, either paclitaxel protein-bound 100 mg/m2 on days 1, 8, and 15 every 28 days; or paclitaxel 90 mg/m2 on days 1, 8, and 15 every 28 days; or gemcitabine 1000 mg/m2 plus carboplatin area under the curve 2 mg/mL/min on days 1 and 8 every 21 days should be administered via intravenous infusion.
Of note, this application was granted accelerated approval based on PFS. However, continued approval for this indication may be dependent upon verification and description of clinical benefit in the confirmatory trials.
The FDA also approved the PD-L1 IHC 22C3 pharmDx as a companion diagnostic for selecting patients with TNBC whose tumors express PD-L1 with a CPS of 10 or higher.2
Currently, PD-L1 IHC 22C3 pharmDx is the only companion diagnostic that is FDA approved to assist in the identification of patients with TNBC who would benefit from treatment with pembrolizumab in combination with chemotherapy. This marks the seventh cancer type for which PD-L1 IHC 22C3 pharmDx has been granted FDA approval; the diagnostic also helps physicians identify patients with non–small cell lung cancer, gastric or gastroesophageal junction adenocarcinoma, esophageal squamous cell carcinoma, cervical cancer, urothelial carcinoma, and head and neck squamous cell carcinoma who would benefit.