Immune checkpoint inhibitors in EGFR-mutant non-small cell lung cancer: A systematic review

•Immune checkpoint inhibitors (ICIs) have limited benefit in EGFR-mutant NSCLC.•A systematic review on ICI-based regimens in this setting was performed.•The available evidence do not support the use of ICIs in pts with EGFR-mutant NSCLC.•Combinations of ICIs, chemo, and antiangiogenic drugs may have role in this setting.•Novel combinations acting on TME are explored to refine potential role of ICIs. Since their first introduction in clinical practice, immune checkpoint inhibitors showed limited benefit in patients with NSCLC harboring EGFR mutations. With the rationale of increasing immune activation, combinatorial ICI strategies have been evaluated also in this subgroup of patients. We performed a systematic review on efficacy of ICI-based strategies in EGFR-mutant NSCLC according to most updated evidence. Overall, ICI monotherapy and ICI plus chemotherapy confirm to be ineffective in EGFR-mutant NSCLC, whereas the combination of ICI with antiangiogenic and chemotherapy showed promising results. Limited data are available with alternative ICI combination strategies, driven by strong biological rationale of modulating the tumor immune microenvironment. To date, the available evidence do not support the use of ICI in patients with NSCLC harboring EGFR mutations. Clinical trials are ongoing to define which is the best timing and exploring novel combinations with ICI in this specific disease.