Objective:

To explore therapeutic strategies for advanced NSCLC with high PD-L1 expression and MET exon 14 skipping mutations, particularly focusing on overcoming immunotherapy resistance.

Key Findings:

• Initial treatment with Tislelizumab resulted in 7 months of progression-free survival, indicating its initial effectiveness.
• Switching to Savolitinib led to significant tumor reduction, demonstrating the potential of targeted therapy.
• Reintroducing Tislelizumab after Savolitinib was discontinued due to liver injury successfully controlled the disease, suggesting a possible strategy for overcoming resistance.

Interpretation:

Sequential treatment with MET inhibitors may restore sensitivity to immunotherapy in patients with high PD-L1 and METex14 mutations, suggesting a novel therapeutic strategy that modifies the tumor microenvironment to enhance treatment efficacy.

Limitations:

• Single case study limits generalizability of findings.
• Lack of established guidelines for managing dual-positive NSCLC cases.
• Need for larger studies to validate findings and establish treatment protocols.

Conclusion:

This case highlights the potential for personalized treatment strategies in NSCLC with complex molecular profiles, advocating for further research into combination therapies and the mechanisms of resistance.