AI Article Synopsis
- The treatment for metastatic renal cell carcinoma (mRCC) is evolving and currently includes a mix of therapies, leading to the need for genomic markers to predict patient responses to these treatments.* -
- This study analyzed tumor tissue from 79 mRCC patients, using targeted sequencing to identify genetic alterations and correlate them with progression-free survival (PFS) on VEGF targeted therapy.* -
- Results indicated that the absence of VHL mutations, along with specific alterations in TP53 and FLT1, is linked to poorer PFS, suggesting a composite model of these genomic markers could help better predict treatment outcomes.*
Article Abstract
Background: First-line treatment for metastatic renal cell carcinoma (mRCC) is rapidly changing. It currently includes VEGF targeted therapies (TT), multi-target tyrosine kinase inhibitors (TKIs), mTOR inhibitors, and immunotherapy. To optimize outcomes for individual patients, genomic markers of response to therapy are needed. Here, we aim to identify tumor-based genomic markers of response to VEGF TT to optimize treatment selection.
Methods: From an institutional database, primary tumor tissue was obtained from 79 patients with clear cell mRCC, and targeted sequencing was performed. Clinical outcomes were obtained retrospectively. Progression-free survival (PFS) on first-line VEGF TT was correlated to genomic alterations (GAs) using Kaplan-Meier methodology and Cox proportional hazard models. A composite model of significant GAs predicting PFS in the first-line setting was developed.
Results: Absence of VHL mutation was associated with inferior PFS on first-line VEGF TT. A trend for inferior PFS was observed with GAs in TP53 and FLT1 C/C variant. A composite model of these 3 GAs was associated with inferior PFS in a dose-dependent manner.
Conclusion: In mRCC, a composite model of TP53 mutation, wild type VHL, and FLT1 C/C variant strongly predicted PFS on first-line VEGF TT in a dose-dependent manner. These findings require external validation.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6347137 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0210415 | PLOS |
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