To Stop or Not to Stop: Is It Time to Reevaluate Immunotherapy Duration in Advanced/Metastatic NSCLC?

Immunotherapy has transformed the treatment landscape of advanced and metastatic non-small cell lung cancer, providing durable survival benefits for a subset of patients. Despite widespread adoption of immune checkpoint inhibitors as frontline therapy, the optimal duration of treatment remains uncertain. Current practice often limits therapy to 2 years or continues indefinitely until progression based on landmark clinical trials that arbitrarily chose these timepoints, and it is not biologically based. Unfortunately, there is still limited prospective or clinical trial evidence to guide such decisions. Retrospective studies have suggested that discontinuation at 2 years may not compromise outcomes, but also raise concerns about balancing efficacy with cumulative toxicities and financial burden. This review provides updated data and ongoing trials seeking to answer these questions, along with potential emerging biomarkers, including circulating tumor DNA (ctDNA) and imaging with positron emission tomography/computed tomography that can help risk-stratify and guide and refine treatment strategies.