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FDA approves Keytruda for first-line treatment of PD-L1–expressing metastatic NSCLC
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The FDA granted approval to pembrolizumab for the first-line treatment of patients with metastatic non–small cell lung cancer whose tumors express programmed death ligand-1 as determined by an FDA–approved test.
This indication applies to patients with no EGFR or ALK genomic tumor aberrations, with high programmed death ligand-1 (PD-L1) expression (tumor proportion score 50%) and who have not received prior systemic chemotherapy for metastatic NSCLC.
“Pembrolizumab (Keytruda, Merck) improved survival, compared to traditional chemotherapy, in patients with NSCLC whose tumors express high levels of PD-L1,” Roger M. Perlmutter, MD, PhD, president of Merck Research Laboratories, said in a company-issued press release. “The approval of pembrolizumab for the first-line treatment of metastatic non-small cell lung cancer has the potential to change the treatment landscape for these patients.”
The approval also expands the second-line indication of pembrolizumab to include all patients with PD-L1 expression. Previously, the agent was only approved in the second-line setting for patients with at least 50% PD-L1 expression. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA–approved therapy indicated for these aberrations prior to receiving pembrolizumab.
Two randomized, controlled trials demonstrated statistically significant improvements in PFS and OS for patients randomly assigned to pembrolizumab compared with chemotherapy.
In a trial of 305 patients who had no prior treatment for metastatic NSCLC whose tumors have high PD-L1 expression, patients treated with pembrolizumab achieved longer median PFS than patients assigned platinum-based chemotherapy (10.3 months vs. 6 months; HR = 0.5; 95% CI, 0.37-0.68).
In addition, a prespecified interim analysis showed pembrolizumab improved OS (HR = 0.6; 95% CI, 0.41-0.89).
In a three-arm trial of 1,033 patients who were previously treated for metastatic NSCLC and whose tumors expressed PD-L1 with a tumor proportion score of at least 1%, pembrolizumab extended survival among patients randomly assigned 2-mg/kg doses every 3 weeks (10.4 months; HR = 0.71; 95% CI, 0.58-0.88) or 10-mg/kg doses every 3 weeks (12.7 months; HR = 0.61; 95% CI, 0.49-0.75) compared with patients assigned docetaxel (8.5 months).
The most common adverse events associated with pembrolizumab included decreased appetite, fatigue, nausea, dyspnea, cough and constipation. Serious adverse events occurred rarely and included immune-mediated pneumonitis, colitis, hepatitis, endocrinopathies and nephritis.
With this new indication, pembrolizumab is the only anti–PD-1 therapy to be approved in the first-line setting for this patient population.
Pembrolizumab is approved for use at a fixed dose of 200 mg every 3 weeks until disease progression, unacceptable toxicity, or for 24 months in patients without disease progression.
“With this new indication, pembrolizumab can now be a first treatment option instead of chemotherapy for patients with metastatic non–small cell lung cancer whose tumors express high levels of PD-L1,” Roy S. Herbst, MD, PhD, professor of medicine and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital at Yale New Haven, said in a press release.
“These data reaffirm the importance of testing for PD-L1 expression in NSCLC in order to identify those patients who are most likely to benefit from treatment with pembrolizumab.”