Anticipating EGFR Targeting in Early Stages of Lung Cancer: Leave No Stone Unturned.

Background: The current treatment landscape of early stage lung cancer is rapidly evolving, particularly in EGFR mutant non-small cell lung cancer (NSCLC), where target therapy is moving to early stages. In the current review, we collected the available data exploring the impact of EGFR targeting in both neoadjuvant and adjuvant settings, underlying lights and shadows and discussing the existing open issues. Methods: We performed a comprehensive search using PubMed and the proceedings of major international meetings to identify neoadjuvant/adjuvant trials with EGFR tyrosine kinase inhibitors (TKIs) in NSCLC. Results: Limited data are available so far about the activity/efficacy of neoadjuvant TKIs in EGFR mutant NSCLC, with only modest downstaging and pathological complete response rates reported. Differently, the ADAURA trial already proposed osimertinib as a potential new standard of care in resected NSCLC harboring an activating EGFR mutation. Conclusion: Anticipating targeted therapy to early stage EGFR mutant NSCLC presents great opportunities but also meaningful challenges in the current therapeutic/diagnostic pathway of lung cancer care. Appropriate endpoint(s) selection for clinical trials, disease progression management, patients' and treatment selection, as well as need to address the feasibility of molecular profiling anticipation, represent crucial issues to face before innovation can move to early stages.