New PDL1 inhibitors for non-small cell lung cancer: focus on pembrolizumab

The advent of immune-checkpoint inhibitors during the past decade represents a major advancement in the treatment of non-small cell lung cancer (NSCLC) with personalized treatment. Platinum-based chemotherapy has reached its efficacy threshold, with its use remaining limited by its toxicity. For NSCLC, inhibitors of the PD1 protein and its ligand PDL1 show promising clinical activity and induce durable responses in patients with advanced disease. The US Food and Drug Administration has approved pembrolizumab for treatment-naive metastatic NSCLC with >50% of tumor cells expressing PDL1 and for metastatic NSCLC with >1% PDL1 expression after progression following first-line platinum-based doublet chemotherapy. In 2017, it also authorized the first-line combination of pembrolizumab and carboplatin-pemetrexed chemotherapy without selection based on PDL1 expression, but European health authorities are still waiting for the results of a Phase III trial. In this review, the clinical results of published and ongoing studies evaluating pembrolizumab for advanced NSCLC are analyzed and the potential role of PDL1 as a factor predictive of overall responses addressed.