FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Nona??Small Cell Lung Cancer: Firsta??Line Therapy and Beyond

摘要

On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic nona??small cell lung cancer (mNSCLC) whose tumors express programmed deatha??ligand 1 (PDa??L1) as determined by an FDAa??approved test, as follows: (a) firsta??line treatment of patients with mNSCLC whose tumors have high PDa??L1 expression (tumor proportion score [TPS] a?￥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PDa??L1 (TPS a?￥1%), with disease progression on or after platinuma??containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDAa??approved therapy for these aberrations prior to receiving pembrolizumab. Approval was based on two randomized, opena??label, activea??controlled trials demonstrating statistically significant improvements in progressiona??free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTEa??024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41a??0.89; pa??=a??.005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37a??0.68; pa??a??.001). In KEYNOTEa??010, patients with disease progression on or after platinuma??containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58a??0.88), pa??a??.001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49a??0.75), pa??a??.001 comparing pembrolizumab 10 mg/kg with chemotherapy. Implications for Practice. This is the first U.S. Food and Drug Administration approval of a checkpoint inhibitor for firsta??line treatment of lung cancer. This approval expands the pembrolizumab indication in seconda??line treatment of lung cancer to include all patients with programmed deatha??ligand 1a??expressing nona??small cell lung cancer.