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A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Multi-institutional Analysis of Immune-Oncology Combination Therapy for Metastatic MiT Family Translocation Renal
Yasser Ged1, Amina Touma1, Luis Meza Contreras2
1Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD.
Summary:
Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear. We conducted a retrospective analysis of IO combinations in mtRCC patients at 4 institutions. Eligible patients had confirmed mtRCC by genitourinary pathologist and received IO combination therapy (IO+IO or IO+VEGF-TKI). Clinical data and treatment outcomes were recorded from the start of systemic therapy. Objective response rate (ORR) was retrospectively evaluated, and time to treatment failure (TTF), and overall survival (OS) were compared for IO+IO and IO+VEGF-TKI groups. We identified 22 mtRCC patients who received IO combinations, all confirmed to have TFE3 rearrangement by FISH. Most patients were female (68%) with a median age of 41 years (16-79). Treatment breakdown included: IO+IO (n=8, 36%) and IO+VEGF-TKI (n=14, 64%). In the evaluable patients for the efficacy analysis, ORR was 14% (1/7) for the IO+IO group and 54% (6/11) for the IO+VEGF-TKI group. With a median follow-up of 32.4 months, the median TTF was 1.2 months and 6.2 months in the IO+IO and IO+VEGF-TKI groups, respectively ( P =0.12). There was no statistically significant difference in median OS between both groups, 36.7 months in the IO+IO group and 15.6 months in IO+VEGF-TKI ( P =0.9). Our findings demonstrate that IO+VEGF-TKI resulted in higher ORR and TTF point estimates without statistically detectable differences, compared with IO+IO therapy. Larger studies are needed to validate these findings and optimize treatment selection.
Insights
Combining immune-oncology (IO) with VEGF-tyrosine kinase inhibitors (TKI) showed higher response rates in metastatic translocation renal cell carcinoma (mtRCC) compared to dual IO therapy. Further research is needed to confirm these findings for mtRCC treatment selection.
Area of Science:
- Oncology
- Genitourinary Cancers
- Translational Research
Background:
- Metastatic translocation renal cell carcinomas (mtRCCs) are rare, aggressive, and have limited therapeutic options.
- Immune-oncology (IO) combinations show promise in mtRCC, but comparisons between dual IO and IO plus VEGF-TKI are lacking.
Purpose of the Study:
- To compare the effectiveness of dual immune-oncology (IO+IO) versus immune-oncology plus VEGF-tyrosine kinase inhibitor (IO+VEGF-TKI) combinations in patients with metastatic translocation renal cell carcinoma (mtRCC).
- To evaluate objective response rate (ORR), time to treatment failure (TTF), and overall survival (OS) for different IO combination strategies in mtRCC.
Main Methods:
- Retrospective analysis of 22 mtRCC patients with confirmed TFE3 rearrangement treated with IO combinations (IO+IO or IO+VEGF-TKI) across four institutions.
- Clinical data and treatment outcomes were collected, including ORR, TTF, and OS.
- Statistical comparison of efficacy endpoints between the IO+IO and IO+VEGF-TKI treatment groups.
Main Results:
- The IO+VEGF-TKI group demonstrated a higher objective response rate (54%) compared to the IO+IO group (14%).
- Median time to treatment failure was longer in the IO+VEGF-TKI group (6.2 months) versus the IO+IO group (1.2 months), though not statistically significant (P=0.12).
- No statistically significant difference in median overall survival was observed between the two treatment groups.
Conclusions:
- IO plus VEGF-TKI combinations may offer improved objective response rates and time to treatment failure in mtRCC compared to dual IO therapy.
- While point estimates suggest a benefit for IO+VEGF-TKI, statistically significant differences in survival were not detected.
- Larger prospective studies are necessary to validate these findings and guide optimal treatment selection for mtRCC patients.
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