Immune checkpoint inhibitors in non-small-cell lung cancer: current status and future directions

Area of Science:

• Oncology
• Immunology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized non-small-cell lung cancer (NSCLC) treatment since 2015.
• Nivolumab, pembrolizumab, and atezolizumab are FDA-approved ICIs for NSCLC.
• Combining ICIs with chemotherapy, radiotherapy, antivascular therapy, and targeted therapy is crucial.

Purpose of the Study:

• To review current and emerging drugs targeting the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) pathways.
• To summarize reported and ongoing clinical trials for these immunotherapies in NSCLC.
• To address challenges in biomarker-driven patient selection and optimizing the efficacy-safety balance.

Main Methods:

• Literature review of clinical trials involving PD-1/PD-L1 and CTLA-4 inhibitors.
• Analysis of FDA-approved ICIs for NSCLC.
• Examination of combination therapy strategies.

Main Results:

• Seven drugs targeting PD-1/PD-L1 and CTLA-4 pathways are currently in clinical use or expected to enter treatment.
• Numerous clinical trials, both completed and recruiting, have been reported for these agents.
• Key challenges include identifying predictive biomarkers and managing the trade-off between treatment effectiveness and adverse events.

Conclusions:

• ICIs represent a significant advancement in NSCLC therapy.
• Future research should focus on personalized treatment selection through biomarkers and refining combination strategies to maximize benefits while ensuring patient safety.