Objective:

To evaluate the relative efficacy and safety of various therapeutic strategies for unresectable stage III EGFR-mutated non-small cell lung cancer (NSCLC).

Approach:

• Study Design: Systematic search of databases for randomized controlled trials (RCTs) and high-quality retrospective studies comparing therapeutic strategies.
• Endpoints: Primary endpoints were progression-free survival (PFS) and overall survival (OS); secondary endpoints included objective response rate (ORR) and safety profiles.
• Analysis Method: Bayesian network meta-analysis (NMA) was performed to calculate hazard ratios (HRs), odds ratios (ORs), and their corresponding 95% credible intervals (CrIs).

Key Findings:

• CRT+EGFR-TKI showed a statistically significant improvement in OS compared to CRT alone (HR = 0.63, 95% CrI: 0.41–0.94).
• EGFR-TKI+RT ranked first for PFS (HR = 0.14, 95% CrI: 0.06–0.33) and had the lowest risk of severe radiation pneumonitis.
• CRT+Durva did not yield a survival benefit and was associated with higher toxicity.

Interpretation:

CRT+EGFR-TKI is the optimal strategy for extending OS in unresectable stage III EGFR-mutated NSCLC, while EGFR-TKI+RT offers a better balance of PFS and tolerability.

Limitations:

• The study's conclusions are based on available RCTs and retrospective studies, which may introduce bias.
• Potential variations in treatment protocols and patient populations across studies could affect generalizability.

Conclusion:

The findings suggest that CRT+EGFR-TKI is preferable for OS, while EGFR-TKI+RT provides improved PFS and tolerability.

Sources:

• Systematic Review Registration