Current front-line treatment strategies in EGFR-mutated advanced NSCLC: Balancing efficacy with risks of interstitial lung disease and venous thromboembolism

Current front-line treatment strategies in EGFR-mutated advanced NSCLC: Balancing efficacy with risks of interstitial lung disease and venous thromboembolismThe therapeutic landscape for patients with previously untreated epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC) has significantly evolved, with novel treatment options now available beyond osimertinib monotherapy.The addition of platinum-pemetrexed chemotherapy to osimertinib has demonstrated improved progression-free survival, particularly in patients with central nervous system metastases.Recently, amivantamab-lazertinib combination has shown superior overall and progression-free survival compared to osimertinib monotherapy in the MARIPOSA trial.However, these efficacy improvements are accompanied by increased toxicity.Interstitial lung disease (ILD) remains a class effect across EGFR-targeted therapies, whereas venous thromboembolism (VTE) has emerged as a notable safety concern specifically associated with amivantamablazertinib combination.Although prophylactic strategies can reduce the risk of these complications, their impact on patients' quality of life and the ability to continue treatment must be carefully considered.Individualized treatment decisions, based on clinical features such as CNS involvement, tumor burden, and patient frailty, are essential to optimize therapeutic outcomes while minimizing adverse effects.This article highlights the evolving first-line treatment strategies in EGFR-mutated advanced NSCLC, with a particular focus on ILD and VTE risks.