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Biomarker analysis from CheckMate 214: nivolumab plus ipilimumab versus sunitinib in renal cell carcinoma
Robert J Motzer1, Toni K Choueiri2, David F McDermott3
1Kidney Cancer Section, Memorial Sloan Kettering Cancer Center, New York, New York, USA motzerr@mskcc.org.
Background:
The phase 3 CheckMate 214 trial demonstrated higher response rates and improved overall survival with nivolumab plus ipilimumab versus sunitinib in first-line therapy for advanced clear-cell renal cell carcinoma (RCC). An unmet need exists to identify patients with RCC who are most likely to benefit from treatment with nivolumab plus ipilimumab.
Methods:
In exploratory analyses, pretreatment levels of programmed death ligand 1 were assessed by immunohistochemistry. Genomic and transcriptomic biomarkers (including tumor mutational burden and gene expression signatures) were also investigated.
Results:
Biomarkers previously associated with benefit from immune checkpoint inhibitor-containing regimens in RCC were not predictive for survival in patients with RCC treated with nivolumab plus ipilimumab. Analysis of gene expression identified an association between an inflammatory response and progression-free survival with nivolumab plus ipilimumab.
Conclusions:
The exploratory analyses reveal relationships between molecular biomarkers and provide supportive data on how the inflammation status of the tumor microenvironment may be important for identifying predictive biomarkers of response and survival with combination immunotherapy in patients with RCC. Further validation may help to provide biomarker-driven precision treatment for patients with RCC.
Insights
Identifying biomarkers for advanced clear-cell renal cell carcinoma (RCC) is crucial. Exploratory analyses suggest tumor inflammation may predict response to nivolumab plus ipilimumab immunotherapy.
Area of Science:
- Oncology
- Immunotherapy
- Biomarker Discovery
Background:
- The CheckMate 214 trial showed improved survival with nivolumab plus ipilimumab for advanced clear-cell renal cell carcinoma (RCC).
- A need exists to identify patients who will benefit most from this combination immunotherapy.
- Predictive biomarkers for this treatment in RCC are currently lacking.
Purpose of the Study:
- To explore potential molecular biomarkers for predicting response to nivolumab plus ipilimumab in advanced clear-cell RCC.
- To investigate the role of tumor microenvironment inflammation in treatment outcomes.
Main Methods:
- Exploratory analysis of pretreatment programmed death ligand 1 (PD-L1) levels via immunohistochemistry.
- Genomic and transcriptomic analyses, including tumor mutational burden and gene expression signatures.
- Correlation of biomarkers with overall survival and progression-free survival.
Main Results:
- Previously identified biomarkers for immune checkpoint inhibitors were not predictive in this RCC cohort.
- Gene expression analysis revealed an association between inflammatory response and progression-free survival.
- No specific pretreatment biomarkers reliably predicted survival outcomes.
Conclusions:
- Exploratory analyses highlight the potential importance of tumor microenvironment inflammation.
- Further validation of inflammation-related biomarkers could enable precision medicine for RCC patients.
- Biomarker-driven treatment selection may optimize outcomes for advanced clear-cell RCC.
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