Exploration of immunotherapy modalities in stage III unresectable non-small cell lung cancer (Review).

In recent years, the treatment of stage III unresectable non-small cell lung cancer (NSCLC) has witnessed notable progress due to the application of immune checkpoint inhibitors, which markedly improved patient prognosis. On the basis of pivotal studies such as PACIFIC and GEMSTONE-301, immune consolidation therapy has become the standard regimen. Durvalumab consolidation therapy extended the median progression-free survival (mPFS) from 5.6 to 16.9 months [hazard ratio (HR)=0.55] and the median overall survival from 29.1 to 47.5 months (HR=0.72), thus increasing the 5-year survival rate by ~10%. Sugemalimab demonstrated similar benefits (mPFS, 9.0 vs. 5.8 months; HR=0.64). Currently, immune consolidation therapy serves as the core treatment strategy, whereas induction therapy and treatment de-escalation strategies provide novel options for specific patient populations. The optimization of treatment sequencing is being integrated with dynamic circulating tumor DNA (ctDNA) monitoring. ctDNA clearance after chemoradiotherapy indicates further remission and notably improved survival outcomes. Furthermore, emerging therapeutic modalities such as antibody-drug conjugates and bispecific antibodies are potentially expected to further reshape the treatment landscape in the future. The present review aimed to provide an evidence-based framework for individualized precision treatment for stage III unresectable NSCLC.