What do we know about the role of neoadjuvant targeted therapy in early-stage EGFR-mutant and ALK-fused non-small cell lung cancer?—a narrative review of the current literature

Background and Objective: The standard first-line treatment for patients with advanced non-small cell lung cancer '(NSCLC)' harbouring epidermal growth factor receptor '(EGFR)' mutations or anaplastic lymphoma kinase '(ALK)' fusions is targeted therapy using tyrosine kinase inhibitors (TKIs). However, data are still lacking on the use of TKIs as a neoadjuvant or induction approach. Therefore, this narrative review aims to summarize the current knowledge on resectable 'EGFR-mutant' and 'ALK-fused' NSCLC regarding available perioperative treatment regimens and off-label neoadjuvant use of targeted therapy. Methods: The relevant literature was identified by using PubMed and ClinicalTrials.gov (last search phase June 2024) and was restricted to English language. Peer-reviewed manuscripts but also conference abstracts that did not undergo peer-review were included. Key Content and Findings: Patients with 'EGFR-mutations' and 'ALK-fusions' have typically been excluded from available phase III perioperative immunotherapy trials due to lower efficacy and higher toxicity of immunotherapy in those patients. In the adjuvant setting, recent evidence from the phase III ALINA and ADAURA trials demonstrated efficacy and safety of targeted therapy in resected 'ALK-fused' and 'EGFR-mutant' NSCLC. However, to date there is no approval for the use of TKIs as neoadjuvant or induction therapy in those patients. We have therefore identified a number of case series and phase II trials using targeted therapy in resectable 'EGFR-mutant' and 'ALK-fused' NSCLC. Conclusions: Current evidence suggests that targeted therapies might be effective in patients with resectable 'EGFR-mutant' and 'ALK-positive' NSCLC, but ongoing trials will need to provide further evidence on the safety and efficacy of perioperative TKI therapy.