Journal
JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
Volume 14, Issue 7, Pages 820-+Publisher
HARBORSIDE PRESS
DOI: 10.6004/jnccn.2016.0086
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Funding
- GlaxoSmithKline
- Roche
- Ventana
- Syapse
- Novartis
- Pfizer
- Astellas Pharma
- Pierre-Fabre
- Millennium
- Sanofi
- Prometheus
- Genentech
- Bristol-Myers Squibb
- Merck
- Foundation Medicine
- Exelixis
- TRACON Pharma
- Trust family at Dana-Farber Cancer Institute
- Loker Pinard at Dana-Farber Cancer Institute
- Michael Brigham Funds for Kidney Cancer Research at Dana-Farber Cancer Institute
- Dana-Farber/Harvard Cancer Center Kidney Cancer Program
- Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE [P50 CA101942-01]
- Kidney Cancer Association
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Advances in next-generation sequencing have provided a unique opportunity to understand the biology of disease and mechanisms of sensitivity or resistance to specific agents. Renal cell carcinoma (RCC) is a heterogeneous disease and highly variable clinical responses have been observed with vascular endothelial growth factor (VEGF)-targeted therapy (VEGF-TT). We hypothesized that whole-exome sequencing analysis might identify genotypes associated with extreme response or resistance to VEGF-TT in metastatic (mRCC). Patients with mRCC who had received first-line sunitinib or pazopanib and were in 2 extreme phenotypes of response were identified. Extreme responders (ERs) were defined as those with partial response or complete response for 3 or more years (n=13) and primary refractory patients (PRPs) were defined as those with progressive disease within the first 3 months of therapy (n=14). International Metastatic RCC Database Consortium prognostic scores were not significantly different between the groups (P=. 67). Considering the genes known to be mutated in RCC at significant frequency, PBRM1 mutations were identified in 7 ERs (54%) versus 1 PRP (7%) (P=.01). In addition, mutations in TP53 (n=4) were found only in PRPs (P=.09). Our data suggest that mutations in some genes in RCC may impact response to VEGF-TT.
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