Clinical Scorecard: Assessment of the effectiveness and safety of anti-VEGF/VEGFR monotherapy versus its combination with immune checkpoint inhibitors in advanced or metastatic renal cell carcinoma: a network meta-analysis

At a Glance

Key Highlights

• VEGF/VEGFR inhibitors improve objective response rate and progression-free survival but resistance and toxicity limit monotherapy efficacy.
• Combination of immune checkpoint inhibitors (ICIs) with anti-VEGF therapies enhances anticancer activity and survival benefits compared to monotherapy.
• Safety profiles differ among regimens; combination therapies may increase grade ≥3 adverse events, complicating treatment selection.

Guideline-Based Recommendations

Diagnosis

• Diagnosis based on clinical, pathological, and staging criteria for RCC including metastatic assessment.

Management

• Use VEGF/VEGFR-targeted therapies (TKIs, monoclonal antibodies) as systemic treatment for aRCC.
• Consider combination therapy of ICIs with anti-VEGF agents to improve efficacy in advanced/metastatic RCC.
• Individualize treatment selection based on patient risk stratification (e.g., IMDC risk groups) and toxicity profiles.

Monitoring & Follow-up

• Monitor for treatment-related adverse events, especially hypertension, fatigue, proteinuria, and hand-foot syndrome.
• Assess progression-free survival and overall survival to evaluate treatment effectiveness.

Risks

• Combination therapies may have higher incidence of grade ≥3 treatment-related adverse events compared to monotherapy.
• Potential for resistance development during anti-VEGF monotherapy.
• Toxicity profiles vary significantly among different regimens, requiring careful patient monitoring.

Patient & Prescribing Data

Patients with advanced or metastatic renal cell carcinoma, including diverse risk groups and ethnic populations (e.g., Asian patients).

Combination of ICIs with VEGF/VEGFR inhibitors shows superior efficacy but with increased toxicity; treatment choice should balance benefits and risks.

Clinical Best Practices

• Incorporate patient risk stratification (IMDC criteria) when selecting first-line therapy.
• Consider combination regimens for improved survival outcomes in appropriate patients.
• Closely monitor and manage adverse events to maintain treatment adherence and quality of life.
• Stay updated with evolving clinical trial data and guideline recommendations to optimize individualized treatment.

References

• Global Cancer Statistics 2025
• NCCN Guidelines for Kidney Cancer
• PRISMA-NMA Guidelines
• CLEAR Trial
• CheckMate 9ER Trial
• KEYNOTE-426 Trial
• RENOTORCH Trial