Monotherapy in EGFR-Mutated Non–Small Cell Lung Cancer

In recent years, the treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) have seen significant advancements, with combination therapies becoming the standard of care in the first-line metastatic setting. A trial called FLAURA2 revealed that combining osimertinib with platinum-pemetrexed led to a better median overall survival of 47.5 months compared to osimertinib monotherapy, which had a median survival of 37.6 months (HR for death 0.77, 95% CI 0.61-0.96, P = .02).

Another trial, MARIPOSA, found that combining amivantamab and lazertinib with osimertinib resulted in a median overall survival of 36.7 months, compared to 36.7 months for osimertinib monotherapy (HR for death 0.75, 95% CI 0.61-0.92, P = .005). However, these combination therapies are associated with a higher risk of side effects and a more complex treatment regimen, while osimertinib monotherapy is convenient and well-tolerated.

This raises the question of whether all patients need intensified treatment or if some may still benefit from osimertinib alone, avoiding the toxic effects of combination therapies. The issue is further complicated by the fact that one-third of patients receiving their first course of osimertinib monotherapy do not receive second-line therapy in clinical trials or real-world settings, often due to deterioration at progression.