Abstract
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.
Highlights
Lung cancer is the leading cause of cancer-related mortality worldwide, and more than 1.5 million deaths are related to lung cancer every year [1]
While the molecular profiling of non-small cell lung cancer (NSCLC) is considered a standard of care in the advanced setting, the utility and necessity of molecular testing in early stage NSCLC are currently coming under the spotlight
The purpose of this review is to summarize the available data about Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) in early stages NSCLC and the rationale supporting early disease profiling
Summary
Lung cancer is the leading cause of cancer-related mortality worldwide, and more than 1.5 million deaths are related to lung cancer every year [1]. The FLAURA trial established osimertinib, a third-generation TKI, as a standard of care in the upfront setting of metastatic NSCLC harboring classical EGFR mutations [10]. As it happened previously for the FLAURA trial, the recent results of the ADAURA study shook the lung cancer oncological scientific community, potentially leading to the anticipation of osimertinib in the adjuvant setting [11]. While the molecular profiling of NSCLC (including the EGFR testing) is considered a standard of care in the advanced setting, the utility and necessity of molecular testing in early stage NSCLC are currently coming under the spotlight. We aim to explore the controversies beneath these trials in order to discuss if the theory of the best first will be (again) the best choice
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