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

Area of Science:

• Oncology
• Immunotherapy
• Thoracic Surgery

Background:

• Stage III unresectable non-small cell lung cancer (NSCLC) treatment has advanced with immune checkpoint inhibitors.
• Immune consolidation therapy, supported by studies like PACIFIC and GEMSTONE-301, is now a standard regimen.

Purpose of the Study:

• To provide an evidence-based framework for individualized precision treatment in stage III unresectable NSCLC.
• To review the impact of immune consolidation therapy and emerging strategies.

Main Methods:

• Review of pivotal clinical trials (e.g., PACIFIC, GEMSTONE-301) evaluating immune checkpoint inhibitors.
• Analysis of data on progression-free survival (PFS) and overall survival (OS) with durvalumab and sugemalimab.
• Exploration of novel strategies including induction therapy, de-escalation, ctDNA monitoring, antibody-drug conjugates, and bispecific antibodies.

Main Results:

• Durvalumab consolidation therapy significantly improved mPFS (5.6 to 16.9 months) and mOS (29.1 to 47.5 months), increasing 5-year survival by ~10%.
• Sugemalimab also demonstrated significant benefits in mPFS (9.0 vs. 5.8 months).
• ctDNA clearance post-chemoradiotherapy correlates with improved remission and survival outcomes.

Conclusions:

• Immune consolidation therapy is the core strategy for stage III unresectable NSCLC.
• Induction therapy, de-escalation, and ctDNA monitoring offer personalized treatment options.
• Emerging therapies like antibody-drug conjugates and bispecific antibodies hold future promise.