Zosia Piotrowska, MD, MHS, and Martin Dietrich, MD, PhD, discuss how the treatment landscape for EGFR-mutated non–small cell lung cancer (NSCLC) has evolved from osimertinib monotherapy toward combination approaches, with experts weighing efficacy benefits against toxicity profiles while emphasizing the importance of individualized treatment selection, prophylactic toxicity management, and careful consideration of subsequent therapy options after disease progression.