Is the game over for PD-1 inhibitors in EGFR mutant non-small cell lung cancer?

The immune checkpoint inhibitor pembrolizumab, has been shown to be efficacious and to have significant and durable antitumor activity in a subset of patients with advanced non-small cell lung cancer (NSCLC). Most notably in NSCLC with high expression of the programmed death ligand-1 (PD-L1). Similarly, there is abundant data to support the use of epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line therapy in patients whose tumors harbor EGFR mutations (1). However, these patients will inevitably progress on these targeted agents and there has been strong interest in examining whether immune checkpoint inhibitors could be effective in these patients (2). To date, the data for use of immune checkpoint inhibitors either after EGFR TKIs or in combination with EGFR TKIs has been extremely disappointing (3). Data to support the use of these agents in the front-line setting in EGFR mutant PD-L1 positive NSCLC patients, was encouraging but sparse. While there is ample published data showing that there are associations between PD-L1 expression and EGFR signaling in NSCLC, whether this could affect response to immunotherapy is not well established and the use PD-1 and PD-L1 inhibitors in this clinical setting remains controversial (4). In a recent study, Lisberg et al. examined whether the anti-PD-1 agent, pembrolizumab could be effective in EGFR mutant patients prior to receiving an EGFR TKI (5)