TP53 mutational status is predictive of pazopanib response in advanced sarcomas

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Base Sequence
  • Disease-Free Survival
  • Female
  • Genetic Markers / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation / genetics
  • Pyrimidines / therapeutic use*
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
  • Retinoblastoma Protein / genetics
  • Retrospective Studies
  • Sarcoma / drug therapy*
  • Sequence Analysis, DNA
  • Sulfonamides / therapeutic use*
  • Treatment Outcome
  • Tumor Suppressor Protein p53 / genetics*

Substances

  • Angiogenesis Inhibitors
  • Genetic Markers
  • Pyrimidines
  • Retinoblastoma Protein
  • Sulfonamides
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • pazopanib
  • Receptors, Vascular Endothelial Growth Factor