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Updated: May 7, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Effectiveness of systemic treatments for advanced non-clear cell renal cell carcinoma: a systematic review and
Yaping Zhang1, Jian Chen2, Xiaoyan Wang1
1Department of Oncology, Affliated Xiaoshan Hospital, Hangzhou Normal University, Hangzhou, China.
Background:
Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous group of malignancies with substantial differences in morphology, genetic profiles, clinical behavior, and prognosis. Optimal treatment for nccRCC remains unclear, largely extrapolated from evidence available for clear cell renal cell carcinoma (ccRCC). This study aimed to compare the efficacy of current mainstream drug treatments for nccRCC to provide clinical treatment guidance for advanced cases.
Methods:
We systematically searched PubMed, Embase, and Cochrane databases for trials published up to January 2, 2024, including controlled and single-arm trials. Primary outcomes included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Results:
We selected six randomized controlled trials (RCTs) comparing mammalian target of rapamycin inhibitors (mTORi) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). These trials included four first-line and two second-line studies, with a total of 398 advanced nccRCC patients. Pooled results showed that VEGFR-TKIs significantly improved PFS compared to mTORi in first-line treatment (relative risk [RR] = 1.387; 95% confidence interval [CI]: 1.04-1.85; p = 0.026). In a single-arm meta-analysis, we included 22 VEGFR-TKI trials, three mTORi trials, 12 immune checkpoint inhibitor (ICI) therapies, five chemotherapy trials, and 10 combination therapy trials. The pooled ORR ranged from 6% (95% CI: 0-16%) to 36% (95% CI: 27-44%), and the pooled DCR ranged from 54% (95% CI: 50-58%) to 81% (95% CI: 70-91%). Subgroup analysis of ICI showed a higher ORR in the PD-L1 positive group compared to the PD-L1 negative group (RR = 3.044; 95% CI: 1.623-5.709; p = 0.001).
Conclusion:
This systematic review and meta-analysis demonstrate that VEGFR-TKIs improve PFS in first-line treatment compared to mTORi. The single-arm meta-analysis suggest that combination therapies with different mechanisms result in better ORR and DCR. Furthermore, PD-L1 positive patients showed significantly better therapeutic responses with ICI treatment than PD-L1 negative patients.
Insights
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) improve progression-free survival (PFS) in first-line non-clear cell renal cell carcinoma (nccRCC) treatment compared to mammalian target of rapamycin inhibitors (mTORi). Combination therapies and immune checkpoint inhibitors (ICIs) in PD-L1 positive patients show promising response rates.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Non-clear cell renal cell carcinoma (nccRCC) is a diverse cancer with unclear optimal treatment strategies.
- Current treatments are often based on clear cell renal cell carcinoma (ccRCC) evidence.
- This study provides clinical guidance for advanced nccRCC by comparing mainstream drug treatments.
Purpose of the Study:
- To compare the efficacy of current mainstream drug treatments for advanced non-clear cell renal cell carcinoma (nccRCC).
- To provide clinical treatment guidance for nccRCC patients.
- To evaluate overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).
Main Methods:
- Systematic search of PubMed, Embase, and Cochrane databases up to January 2, 2024.
- Inclusion of controlled and single-arm trials.
- Meta-analysis of six randomized controlled trials (RCTs) comparing mammalian target of rapamycin inhibitors (mTORi) and vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs).
- Single-arm meta-analysis of VEGFR-TKI, mTORi, immune checkpoint inhibitor (ICI), chemotherapy, and combination therapy trials.
Main Results:
- VEGFR-TKIs significantly improved PFS over mTORi in first-line treatment (RR = 1.387, p = 0.026).
- Pooled ORR ranged from 6% to 36%, and pooled DCR ranged from 54% to 81%.
- Immune checkpoint inhibitors (ICIs) showed a higher ORR in PD-L1 positive patients compared to PD-L1 negative patients (RR = 3.044, p = 0.001).
Conclusions:
- VEGFR-TKIs enhance PFS in first-line nccRCC treatment compared to mTORi.
- Combination therapies demonstrate improved ORR and DCR.
- PD-L1 positivity is associated with superior therapeutic response to ICIs in nccRCC.
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