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|Ref Type||Journal Article|
|Authors||Koehler K, Liebner D, Chen JL|
|Title||TP53 mutational status is predictive of pazopanib response in advanced sarcomas.|
|Abstract Text||To investigate whether TP53 DNA mutational status impacts progression-free survival (PFS) in patients with advanced sarcomas (soft tissue sarcoma) treated with vascular endothelial growth factor receptors (VEGFR) inhibition.We retrospectively reviewed 19 cases of patients treated at the Ohio State James Comprehensive Cancer Center with advanced sarcoma treated with VEGFR inhibition who also had next-generation sequencing of their tumors (via FoundationOne Heme panel). We evaluated TP53 as well as mutations that were observed in at least 20% of patients and evaluated its contribution to PFS using the Kaplan-Meier survival analysis of available radiology end points.Mutations that were observed in at least 20% of patients included TP53 and Rb1. Only TP53 was predictive of PFS in the context of VEGFR inhibition. The PFS of patients with TP53 mutations was significantly greater than TP53 wild-type tumors with the median PFS of 208 versus 136 days, respectively [P = 0.036, hazards ratio 0.38 (95% confidence interval 0.09-0.83)].Mutations in TP53 may serve as a predictive biomarker of response to VEGFR inhibition in patients with advanced sarcoma. Larger, prospective studies are necessary to confirm these findings.|
|Molecular Profile||Treatment Approach|
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|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
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|TP53 mutant||sarcoma||sensitive||Pazopanib||Clinical Study - Cohort||Actionable||In a retrospective analysis, advanced sarcoma patients with TP53 mutations displayed improved progression-free survival (208 vs 136 days, p=0.036) relative to patients with wild-type TP53 when treated with Votrient (pazopanib) (PMID: 26646755).||26646755|