US FDA approves expanded label for Merck’s Keytruda as first-line treatment for NSCLC

The US Food and Drug Administration (FDA) approved Keytruda’s expanded label as a first-line treatment for patients with metastatic non-squamous non-small cell lung cancer (NSCLC), when administered with the combination of pemetrexed and platinum chemotherapy.

Keytruda, as a combination treatment, was first approved in 2017 for first-line treatment of patients with metastatic nonsquamous NCLSC, under the FDA’s accelerated approval process. Continued approval was contingent upon verification and description of clinical benefit, which was proven in Keynote-189​ – allowing the FDA to approve the label expansion.

The trial results showed statically significant improvement in overall survival with the combination therapy including Keytruda, in comparison to chemotherapy alone. The trial also revealed results that the treatment reduced the risk of death by roughly half when compared to chemotherapy alone.

Progression-free survival rate was also statically significantly improved with the combination therapy.

Keytruda is a humanized monoclonal antibody (mAb) that blocks PD-1 interactions between ligands PD-L2. Merck, known as MSD outside of North America, said that Keytruda is the first anti-PD-1 approved in the first-line setting as both combination and monotherapy in certain patients with metastatic NSCLC. This expanded label will allow for greater use of the treatment.

Merck also stated that they believe physicians will have continued confidence in prescribing Keytruda in combination therapy now that data from Keynote-189 is on the label.

Trials and Keynote-189​

According to Merck, Keynote-189 was a Phase III, randomized, multicenter, double-blind, active-controlled trial in systemic-therapy naïve patients with metastatic NSCLC, regardless of PD-L1 tumor expression status. The study was conducted in collaboration with Eli Lilly, the makers of pemetrexed.

PD-1 combination therapies have shown very complex trial results. We previously reported that two Phase III studies examining Keytruda in combination with other therapies were put on pause after patient deaths​. Keynote-183 and Keynote-185 were paused by Merck in 2017. These trials were not for patients with NSCLC but relapsed or refractory multiple myeloma and treatment naïve forms of blood cancer respectively.