Combining immunotherapy and epidermal growth factor receptor kinase inhibitors: worth the risk?

Immunotherapy has improved survival in advanced non-small cell lung cancer (NSCLC) and offers the potential for meaningful, durable responses in a subset of patients. Ongoing efforts are focused on extending these benefits to more patients. In a recent study, Yang et al. explore combinations of pembrolizumab with either erlotinib or gefitinib with that goal in mind (1). Erlotinib and gefitinib, first generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) were administered concurrently with the anti-PD-1 antibody pembrolizumab in patients with EGFR mutant NSCLC in two cohorts of the KEYNOTE-021 trial. The authors concluded that the combination of erlotinib plus pembrolizumab was tolerable, based on their 19-patient cohort. They felt the combination of gefitinib and pembrolizumab was not tolerable, as 5 out of 7 patients developed grade 3–4 hepatotoxicity. The response rate was high, but consistent with prior EGFR TKI monotherapy studies