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Updated: May 18, 2026
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Retrospective comparison of triple-sequence therapies in metastatic renal cell carcinoma
Jonas Busch1, Christoph Seidel, Barbara Erber
1Department of Urology, Charité University Medicine Berlin, Berlin, Germany.
Background:
The optimal sequence of targeted therapy in patients with metastatic renal cell carcinoma (mRCC) has not been defined.
Objective:
To describe the efficacy and toxicity of the most common sequences of targeted therapy, namely, receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi), in different sequences after failure of vascular endothelial growth factor signaling inhibition (VEGFi) in first-line therapy.
Design, Setting And Participants:
Retrospective study of 103 patients receiving VEGFi-rTKI-mTORi (n=62) or VEGFi-mTORi-rTKI (n=41) at two German academic centers.
Intervention:
Sequence of systemic targeted treatment.
Outcome Measurements And Statistical Analysis:
Response was assessed using Response Evaluation Criteria in Solid Tumors 1.0 and toxicity was measured using the Common Terminology Criteria for Adverse Events 3.0. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Predictors of survival were analyzed using Cox regression.
Results And Limitations:
Sequence groups did not significantly differ by patient characteristics and response rate following first VEGFi failure. Median PFS for second-line therapy was 4.6 mo (95% confidence interval [CI], 3.8-5.4), 4.1 mo (95% CI, 3.4-4.9) for rTKI treatment, and 5.4 mo (95% CI, 2.7-8.1) for mTORi treatment (p=0.400). No differences in PFS were observed among third-line therapy groups (3.6 mo for mTORi; 3.7 mo for rTKI). Treatment duration following first VEGFi failure (combined second- and third-line PFS) was 10.0 mo for VEGFi-rTKI-mTORi and 12.2 mo for VEGFi-mTORi-rTKI (p=0.103). No significant differences in OS were observed among sequence groups (33.7 mo [95% CI, 30.4-37.1] for VEGFi-rTKI-mTORi; 38.7 mo [95% CI, 24.4-52.9] for VEGFi-mTORi-rTKI). Primary resistance on first-line therapy was an independent predictor of OS, but type of sequence was not. Limitations are the retrospective design and limited numbers of cases.
Conclusions:
The sequence therapies VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi with the currently available agents appear to be equally efficacious in terms of PFS, OS, and response rate, with no apparent beneficial effect with an early use of mTORi.
Insights
For metastatic renal cell carcinoma, the sequence of vascular endothelial growth factor signaling inhibition (VEGFi) followed by receptor tyrosine kinase inhibitor (rTKI) and mammalian target of rapamycin inhibitor (mTORi) or vice versa showed similar efficacy. Treatment sequence did not impact overall survival.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- The optimal sequence of targeted therapies for metastatic renal cell carcinoma (mRCC) remains undefined.
- Understanding treatment sequences is crucial for improving patient outcomes in mRCC.
Purpose of the Study:
- To compare the efficacy and toxicity of two common targeted therapy sequences in mRCC patients after first-line vascular endothelial growth factor signaling inhibition (VEGFi) failure.
- Specifically, to evaluate VEGFi-receptor tyrosine kinase inhibitor (rTKI)-mammalian target of rapamycin inhibitor (mTORi) versus VEGFi-mTORi-rTKI sequences.
Main Methods:
- Retrospective analysis of 103 mRCC patients receiving sequential targeted therapies.
- Patients were grouped into VEGFi-rTKI-mTORi (n=62) or VEGFi-mTORi-rTKI (n=41) sequences.
- Progression-free survival (PFS), overall survival (OS), and response rates were assessed using standard criteria and survival analysis methods.
Main Results:
- No significant differences in patient characteristics or response rates were observed between the sequence groups after first-line VEGFi failure.
- Median PFS for second-line therapy was comparable (4.6 months for rTKI vs. 5.4 months for mTORi).
- Overall survival (OS) did not differ significantly between the VEGFi-rTKI-mTORi (33.7 months) and VEGFi-mTORi-rTKI (38.7 months) groups.
Conclusions:
- The sequences VEGFi-mTORi-rTKI and VEGFi-rTKI-mTORi demonstrate similar efficacy in terms of PFS, OS, and response rates for mRCC.
- Early use of mTOR inhibitors does not appear to confer a significant benefit compared to later use within these sequences.
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