Format

Send to

Choose Destination
Ann Oncol. 2016 Mar;27(3):539-43. doi: 10.1093/annonc/mdv598. Epub 2015 Dec 8.

TP53 mutational status is predictive of pazopanib response in advanced sarcomas.

Author information

1
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus.
2
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus Division of Bioinformatics, Department of Biomedical Informatics, The Ohio State University, Columbus, USA.
3
Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus Division of Bioinformatics, Department of Biomedical Informatics, The Ohio State University, Columbus, USA james.chen@osumc.edu.

Abstract

BACKGROUND:

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.

PATIENTS AND METHODS:

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.

RESULTS:

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)].

CONCLUSIONS:

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.

KEYWORDS:

TP53; VEGFR; next-generation sequencing; pazopanib; sarcoma

PMID:
26646755
PMCID:
PMC5006122
[Available on 2017-03-01]
DOI:
10.1093/annonc/mdv598
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center