Positive Phase 3 Results Reported for Keytruda in Patients With Advanced NSCLC

Merck’s immunotherapy demonstrated superior progression-free and overall survival

The KEYNOTE-024 trial investigating the use of Keytruda (pembrolizumab, Merck) in patients with previously untreated advanced non–small-cell lung cancer (NSCLC) has found pembrolizumab superior to chemotherapy for both the primary endpoint of progression-free survival (PFS) and the secondary endpoint of overall survival (OS). Based on these results, an independent data monitoring committee has recommended that the trial be stopped, and that patients receiving chemotherapy be offered the opportunity to receive pembrolizumab.

The KEYNOTE-024 trial—a randomized, pivotal, phase 3 study—evaluated pembrolizumab monotherapy compared to standard-of-care (SOC) platinum-based chemotherapies in the treatment of patients with advanced NSCLC. The 305 patients enrolled had received no prior systemic chemotherapy treatment for their advanced disease and had tumors that expressed high levels of programmed death-ligand 1 (PD-L1) (defined as a tumor proportion score of 50% or more) as determined by a central laboratory using an immunohistochemistry assay.

The study randomized the patients to receive pembrolizumab (200 mg every three weeks) or SOC platinum-based chemotherapies: paclitaxel plus carboplatin, pemetrexed plus carboplatin, pemetrexed plus cisplatin, gemcitabine plus carboplatin, or gemcitabine plus cisplatin. Pemetrexed maintenance therapy was permitted for patients with nonsquamous histologies. In addition, patients randomized to the control had the option of crossing over to pembrolizumab upon disease progression.

The safety profile of pembrolizumab in this trial was consistent with that observed in previously reported studies in patients with advanced NSCLC.

Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. The therapy blocks the interaction between programmed cell death protein 1 (PD-1) and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells.

Pembrolizumab is indicated for the treatment of patients with unresectable or metastatic melanoma. It is also indicated for use in patients with metastatic NSCLC whose tumors express PD-L1 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 indication is approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

Source: Merck; June 16, 2016.