FDA Approves Pembrolizumab for PD-L1-expressing Metastatic NSCLC
The FDA has approved pembrolizumab (Keytruda) for the treatment of patients with metastatic NSCLC whose tumors express PD-L1.
The U.S. Food and Drug Administration (FDA) has approved pembrolizumab (Keytruda) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test.1
The FDA approval added the following 2 indications for pembrolizumab:
- Patients with metastatic NSCLC whose tumors have high PD-L1 expression (Tumor Proportion Score [TPS] greater than or equal to 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 (TPS greater than or equal to 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.
This current approval converts the prior accelerated approval in second-line treatment of patients with metastatic NSCLC to regular approval and expands the indication in second-line treatment to include all patients with PD-L1-expressing NSCLC. It is also the first FDA approval of a checkpoint inhibitor for the frontline treatment of lung cancer.
Approval was based on findings from 2 clinical trials that demonstrated that treatment with pembrolizumab significantly prolonged progression-free survival and overall survival compared with chemotherapy in patients with metastatic NSCLC.
In a trial of 305 treatment-naive patients with a TPS greater than or equal to 50%, pembrolizumab was associated with a 50% reduced risk of progression or death (hazard ratio [HR], 0.50; 95% CI, 0.37-0.68; P < .001) and a 40% reduction in the risk of mortality vs chemotherapy (HR, 0.60; 95% CI, 0.41-0.89; P < .005).
In a 3-arm trial of 1033 previously treated patients with a TPS greater than or equal to 1%, pembrolizumab 2 mg/kg every 3 weeks reduced the risk of death by 29% compared with docetaxel (HR, 0.71; 95% CI, 0.58-0.88; P < .001) and pembrolizumab 10 mg/kg every 3 weeks was associated with a 39% reduction in the risk of death vs chemotherapy (HR, 0.61; 95% CI, 0.49-0.75; P < .001).
The most common adverse events with pembrolizumab among patients with metastatic NSCLC were decreased appetite, fatigue, nausea, dyspnea, cough, and constipation. Clinicians should be aware that pembrolizumab may cause immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
The recommended dose and schedule of pembrolizumab for patients with NSCLC is 200 mg intravenously over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months among patients without disease progression.
- Pembrolizumab (Keytruda) checkpoint inhibitor. U.S. Food and Drug Administration approved drugs website. http://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm526430.htm. Updated October 24, 2016. Accessed October 25, 2016.