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Updated: Mar 15, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
VEGF-TKI Outcomes in Metastatic Renal Cell Carcinoma According to Prior Immune Checkpoint Inhibitor or VEGF-TKI: A
Elizabeth Nally1, Agne Jovaisaite1, Sara Coca Membribes1
1Barts Cancer Institute, NIHR Biomedical Research Centre, Queen Mary University of London, London EC1M 6AU, UK.
Abstract:
Background/Objectives: Most patients with metastatic renal cell carcinoma (mRCC) progress on first-line immune checkpoint inhibitor (ICI). Subsequent vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is standard. Due to the rapid evolution in treatment landscape, data directly comparing outcomes of VEGF-TKI following ICI versus VEGF-TKI alone are limited. This scoping review aimed to explore whether VEGF-TKI following prior ICI is associated with improved outcome, potentially reflecting a treatment sequence effect. Methods: PubMed/MEDLINE and ClinicalTrials.gov were searched systematically to identify phase 2/3 prospective clinical trials that investigated VEGF-TKI in patients who had progressed after ≥1 therapy published from 2004. Included studies were summarised by prior therapy and reported outcomes. Data from subgroups/arms were extracted and weighted overall response rate (ORR), progression free survival (PFS) and overall survival (OS) calculated for patients pretreated with VEGF-TKI versus ICI. An exploratory, hypothesis generating analysis was performed comparing outcomes between patients who received prior VEGF-TKI only or ICI-based therapy. Results: In total, 17 clinical trials were included: 2538 patients had prior VEGF-TKI (15 subgroups/arms) and 724 prior ICI-based therapy (11 subgroups/arms). In prior VEGF-TKI, weighted mORR was 8% (IQR 6-16%) versus 28% (IQR 20-41%) post-ICI. Weighted mPFS was 3.9 m (IQR 3.6-5.4) with prior VEGF-TKI versus 8.3 m (IQR 7.4-10.3) in prior ICI group. Weighted mOS was 15.2 m (IQR 11.1-16.6) versus 22.1 m (IQR 10.9-22.1) with prior ICI. Conclusions: Improved outcomes in ICI pretreated population in this exploratory analysis suggests ongoing biological benefit of ICI therapy. As prospective 2L randomised studies are not feasible, we conclude that VEGF therapy in pretreated mRCC is at least as good, if not better, since the introduction of 1st line ICI.
Insights
Patients with metastatic renal cell carcinoma (mRCC) receiving vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) after immune checkpoint inhibitor (ICI) therapy showed improved outcomes. This suggests a potential benefit from sequencing VEGF-TKI after ICI in mRCC treatment.
Area of Science:
- Oncology
- Clinical Trials
- Cancer Therapeutics
Background:
- Most patients with metastatic renal cell carcinoma (mRCC) progress after first-line immune checkpoint inhibitor (ICI) therapy.
- Subsequent vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI) is a standard treatment approach.
- Limited data exist comparing VEGF-TKI after ICI versus VEGF-TKI alone due to rapid treatment landscape evolution.
Purpose of the Study:
- To explore if VEGF-TKI following prior ICI is associated with improved outcomes in mRCC.
- To investigate potential treatment sequence effects in mRCC therapy.
Main Methods:
- Systematic search of phase 2/3 prospective clinical trials from 2004 onwards in PubMed/MEDLINE and ClinicalTrials.gov.
- Included studies investigated VEGF-TKI in patients progressed after at least one therapy.
- Extracted and analyzed data on overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients pretreated with VEGF-TKI versus ICI.
Main Results:
- 17 clinical trials involving 3262 patients were included (2538 prior VEGF-TKI, 724 prior ICI).
- Weighted mORR was 8% post-VEGF-TKI vs. 28% post-ICI; weighted mPFS was 3.9 months vs. 8.3 months; weighted mOS was 15.2 months vs. 22.1 months.
- Patients pretreated with ICI showed significantly better outcomes (ORR, PFS, OS) compared to those pretreated with VEGF-TKI alone.
Conclusions:
- Improved outcomes in the ICI-pretreated population suggest a potential ongoing biological benefit of ICI therapy.
- VEGF therapy in pretreated mRCC appears to be at least as effective, if not more so, since the introduction of first-line ICI.
- This exploratory analysis supports considering VEGF-TKI after ICI for mRCC patients, given the limitations of prospective randomized trials.
