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TP53 status may predict response to VEGFR inhibition for advanced sarcoma
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The TP53 gene mutation may predict improved response to VEGF receptor inhibition among patients with advanced sarcomas, according to a retrospective chart review.
Prior studies showed pazopanib (Votrient, Novartis), an oral tyrosine kinase inhibitor, improved PFS among patients with metastatic nonadipocytic soft tissue sarcoma.
James L. Chen
Evidence also suggested patients with soft tissue sarcomas who harbor TP53 mutations may respond better to VEGF receptor inhibition than those with TP53 wild-type disease.
James L. Chen, MD, assistant professor of biomedical informatics and internal medicine at The Ohio State University, and colleagues reviewed data from 19 patients (mean age, 49 years) with soft tissue sarcoma treated with pazopanib to determine if TP53 status affected outcomes.
PFS served as the primary endpoint.
Researchers observed 233 mutations in the cohort. They stratified patients by the two most frequently observed mutations, TP53 (n = 10; 53%) and Rb1 (n = 6; 32%).
All TP53 mutations were predicted to be loss-of-function mutations
Eighteen patients received oral pazopanib administered at maximal tolerated doses. One patient received sunitinib (Sutent, Pfizer).
Researchers identified 11 responders among pazopanib-treated patients. One achieved partial remission and 10 demonstrated stable disease.
Patients with TP53 mutations achieved longer median PFS than those with TP53 wild-type tumors (208 days vs. 136 days; HR = 0.38; 95% CI, 0.09-0.83).
The researchers acknowledged the study was limited by its retrospective nature, the small sample size, a wide-range of histologies and its restriction to a single institution.
“Despite this, we observed a significant increase in the PFS of patients with advanced soft tissue sarcoma and TP53 mutations that is hypothesis-generating and supported by the emerging relevance of targeting the p53-VEGF axis as a therapeutic modality in cancer patients,” Chen and colleagues wrote. “Larger correlative studies should be carried out to confirm these results.” — by Kristie L. Kahl
Disclosure: Chen reports an advisory role with Novartis. The other researchers report no relevant financial disclosures.
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