FDA Approves Pembrolizumab as First-Line Treatment for PD-L1–Positive Non–Small Cell Lung Cancer

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On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) for the treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors express programmed cell death ligand 1 (PD-L1) as determined by an FDA-approved test.

This is the first FDA approval of a checkpoint inhibitor for first-line treatment of lung cancer. This approval also expands the indication in second-line treatment of lung cancer to include all patients with PD-L1–expressing NSCLC.

The FDA approval added the following indications for pembrolizumab:

  • Patients with metastatic NSCLC whose tumors have high PD-L1 expression (tumor proportion score ≥ 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations, and no prior systemic chemotherapy treatment for metastatic NSCLC
  • Patients with metastatic NSCLC whose tumors express PD-L1 (tumor proportion score ≥ 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.

Approval was based on results of two randomized, controlled trials that demonstrated statistically significant improvements in progression-free and overall survival for patients randomized to pembrolizumab compared with ­chemotherapy.


In the phase III KEYNOTE-024 trial, 305 patients who had no prior treatment for metastatic NSCLC and tumor proportion score ≥ 50%, those who received pembrolizumab (200 mg every 3 weeks) had a significant improvement in progression-free survival (hazard ratio [HR] = 0.50 [95% confidence interval [CI] = 0.37–0.68]; P < .001) with a median progression-free survival of 10.3 months vs 6.0 months for those receiving platinum-based chemotherapy. A prespecified interim analysis demonstrated a statistically significant improvement in overall survival for patients randomized to pembrolizumab as compared with chemotherapy (HR = 0.60 [95% CI = 0.41–0.89]; P < .005).


In the three-arm phase II/III KEYNOTE-010 trial, 1,033 patients who were previously treated for metastatic NSCLC with a tumor proportion score ≥ 1%, those randomized to pembrolizumab at 2 mg/kg every 3 weeks (HR = 0.71 (95% CI = 0.58–0.88]; P < .001) or pembrolizumab at 10 mg/kg every 3 weeks (HR = 0.61 [95% CI = 0.49–0.75]; P < .001) had an improved overall survival compared with patients receiving docetaxel. The median survival was 10.4 months in the pembrolizumab 2-mg/kg arm, 12.7 months in the pembrolizumab 10-mg/kg arm, and 8.5 months in the docetaxel arm.

The most common side effects of treatment with pembrolizumab included decreased appetite, fatigue, nausea, dyspnea, cough, and constipation. Rare but serious adverse events included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

The recommended dose and schedule of pembrolizumab for NSCLC are 200 mg intravenously every 3 weeks.

The FDA granted pembrolizumab Breakthrough Therapy designation and Priority Review status, and previously granted Accelerated Approval. The current approval converts the prior accelerated approval in second-line treatment of metastatic NSCLC patients to regular approval. The application for the first-line indication was approved nearly 3 months before the Prescription Drug User Fee Act goal date. ■