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FDA Approves Keytruda for First-Line Treatment of Metastatic Lung Cancer

Agency also updates second-line labeling

The FDA has cleared pembrolizumab (Keytruda, Merck), an anti-programmed death receptor-1 (PD-1) therapy, for the first-line treatment of certain patients with metastatic non–small-cell lung cancer (NSCLC).

The new indication applies to patients whose tumors have high programmed death ligand-1 (PD-L1) expression (i.e., a tumor proportion score [TPS] of 50% or more), as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations. With this indication, pembrolizumab is the only anti-PD-1 therapy to be approved in the first-line treatment setting for these patients.

In addition, the FDA approved a labeling update to include data from the KEYNOTE-010 trial in the second-line or greater treatment setting for patients with metastatic NSCLC whose tumors express PD-L1 (TPS of 1% or more), 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 before receiving pembrolizumab.

In metastatic NSCLC, pembrolizumab is approved for use at a fixed dose of 200 mg every three weeks until disease progression or unacceptable toxicity occurs, or up to 24 months in patients without disease progression.

The FDA’s approval of pembrolizumab as a first-line treatment for certain NSCLC patients was based on data from KEYNOTE-024, a phase 3, randomized, open-label study that compared pembrolizumab monotherapy with standard-of-care (SOC) platinum-containing chemotherapy for the treatment of patients with both squamous (18%) and nonsquamous (82%) metastatic NSCLC. The study enrolled patients who had not received systemic chemotherapy treatment for their metastatic disease and whose tumors had high PD-L1 expression (TPS of 50% or more) with no EGFR or ALK aberrations.

KEYNOTE-024 randomly assigned 305 patients to receive pembrolizumab (200 mg every three weeks) or the investigator’s choice of SOC platinum-based chemotherapy (pemetrexed plus carboplatin; pemetrexed plus cisplatin; gemcitabine plus cisplatin; gemcitabine plus carboplatin; or paclitaxel plus carboplatin). Pemetrexed maintenance therapy was permitted for patients with nonsquamous histologies. The study’s primary endpoint was progression-free survival (PFS); additional efficacy outcome measures included overall survival (OS).

Based on interim data indicating that pembrolizumab was superior to chemotherapy for both PFS and OS, the trial was stopped early in June 2016 to give patients still on chemotherapy the opportunity to receive pembrolizumab.

The results demonstrated that pembrolizumab reduced the risk of disease progression or death by 50% compared with chemotherapy (hazard ratio [HR], 0.50; P < 0.001). In addition, treatment with pembrolizumab resulted in a 40% reduction in the risk of death compared with chemotherapy (HR, 0.60; P = 0.005).

Source: Merck; October 24, 2016.

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