Objective:

To systematically compare the efficacy and safety of VEGF/VEGFR-targeted monotherapy against its combination with immune checkpoint inhibitors in patients with advanced or metastatic renal cell carcinoma, addressing current treatment challenges.

Key Findings:

• Combination therapies with immune checkpoint inhibitors show superior efficacy in progression-free survival (PFS) and overall survival (OS) compared to traditional TKI monotherapy, with specific metrics to be detailed.
• Higher incidence of grade ≥ 3 treatment-related adverse events observed with combination therapies.
• Discrepancies in international treatment guidelines regarding the use of combination therapy for low-risk patients.

Interpretation:

The findings suggest that while combination therapies may enhance treatment outcomes, they also come with increased toxicity, necessitating careful patient selection and risk stratification, which is critical for clinical practice.

Limitations:

• Lack of direct head-to-head comparisons among treatment options.
• Previous meta-analyses excluded recent key trials, particularly in Asian populations.
• Efficacy data specific to subgroups remain underexplored, impacting the overall conclusions.

Conclusion:

The study provides a robust evidence-based foundation for individualized treatment strategies in advanced or metastatic renal cell carcinoma, highlighting the need for further exploration of safety profiles and efficacy across different patient populations, particularly in underrepresented groups.