Objective:

To evaluate the efficacy and safety of KRAS G12C inhibitors (KRAS G12Ci) in solid tumors and explore the role of PD-L1 expression in treatment response.

Approach:

• Literature Search: A systematic search was conducted in PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials involving solid tumor patients treated with KRAS G12Ci.
• Data Extraction: Individual participant data on progression-free survival (PFS) and overall survival (OS) were extracted from published Kaplan-Meier survival curves.
• Subgroup Analysis: Subgroup data by PD-L1 expression were extracted to explore immune-related correlates of treatment response.

Key Findings:

• PFS was significantly better in the KRAS G12Ci group (HR, 0.62; P < 0.001).
• No statistical difference in OS was observed (HR, 0.93; P = 0.495).
• Objective response rate (ORR) was 3.60 (95% CI; 2.01-6.46; P < 0.001).
• PFS benefits were observed in patients with PD-L1 expression levels <1% and 1%-49%.
• KRAS G12Ci demonstrated a better safety profile, except for diarrhea and rash.

Interpretation:

Limitations:

• The findings are based on a limited number of studies (4 articles with 3 RCTs).
• Subgroup observations are hypothesis-generating and require prospective validation.

Conclusion:

Sources:

• Systematic Review Registration