The Quest to Cure Metastatic Non-Small Cell Lung Cancer With Immunotherapy

The introduction of immune checkpoint inhibitors targeting the programmed death-1 (PD-1) axis represented a major therapeutic advance, enabling long-term survival, and even cure, in a subset of patients, an outcome previously considered unattainable in metastatic disease. However, most patients do not yet derive sustained benefit. Despite extensive efforts to define biomarkers, identify mechanisms of sensitivity and resistance, and translate these insights into therapeutic strategies, attempts to intensify PD-1-based therapy have failed to improve long-term survival. Extending durable benefit and achieving cure in a broader population will require a deeper understanding of mechanisms of resistance, the development of novel immunotherapeutics, and more precise personalization of treatment strategies.