Expression of p53 as a biomarker of pazopanib efficacy in solitary fibrous tumours: translational analysis of a phase II trial.

Autor:	Napolitano A; Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy., Moura DS; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain., Hindi N; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain., Mondaza-Hernandez JL; Health Research Institute Fundacion Jimenez Diaz, Universidad Autonoma de Madrid (IIS/FJD-UAM), Madrid, Spain., Merino-Garcia JA; Instituto de Investigacion Sanitaria Fundacion Jimenez Diaz, Universidad Autónoma de Madrid, Madrid, Spain., Ramos R; Department of Pathology, University Hospital Son Espases, Palma, Spain., Dagrada GP; Department of Diagnostic Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Stacchiotti S; Department of Cancer Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Graziano F; Medical Oncology Unit, Ospedali Riuniti Marche Nord, Pesaro, Italy., Vincenzi B; Department of Medical Oncology, University Campus Bio-Medico, via Alvaro del Portillo 200, Rome 00128, Italy., Martin-Broto J; University Hospital General de Villalba, Madrid, Spain.
Jazyk:	angličtina
Zdroj:	Therapeutic advances in medical oncology [Ther Adv Med Oncol] 2022 Aug 06; Vol. 14, pp. 17588359221116155. Date of Electronic Publication: 2022 Aug 06 (Print Publication: 2022).
DOI:	10.1177/17588359221116155
Abstrakt:	Background: Solitary fibrous tumours (SFT) are soft tissue sarcomas molecularly defined by the presence of the NAB2::STAT6 intrachromosomal fusion gene. Recently, a prospective phase II trial evaluating the role of the antiangiogenic tyrosine kinase inhibitor pazopanib in SFT has been conducted (NCT02066285). Methods: Here, we analysed the mRNA and protein expression levels of the tumour suppressor and angiogenesis regulator p53 ( TP53 ) in pre-treatment tumour samples from 22 patients with low aggressive (or typical) SFT and 28 patients with high aggressive (26 malignant and 2 dedifferentiated) SFT enrolled in the aforementioned pazopanib phase II trial. These results were correlated with radiological progression-free survival (PFS) and objective response. Univariate and multivariate Cox regression analyses were also performed, including known clinic-pathological prognostic factors. Results: Diffuse immunohistochemistry (IHC) expression of p53 was only found in patients with aggressive SFT and was associated with significantly shorter PFS [hazard ratio (HR): 4.39, 95% confidence interval (CI): 1.19-16.14). TP53 mRNA levels were significantly higher in the low aggressive SFT group. Only in the high aggressive SFT group, relatively higher levels of TP53 were significantly associated with shorter PFS (HR: 4.16, 95% CI: 1.46-11.89) as well as to a lower rate of disease control following treatment with pazopanib. In the multivariate analysis, the only independent prognostic factor in the whole cohort was mitotic count. Conclusion: Diffuse p53 IHC expression and higher TP53 mRNA levels are associated with worse prognosis in the subset of aggressive SFT patients treated with pazopanib. Competing Interests: Competing Interests: AN: reports non-financial and travel support from PharmaMar, Eisai and Lilly DSM: reports institutional research grants from PharmaMar, Eisai, Immix BioPharma and Novartis outside the submitted work; travel support from PharmaMar, Eisai, Celgene, Bayer and Pfizer NH: reports grants, personal fees and non-financial support from PharmaMar, personal fees from Lilly, grants from Eisai, and Novartis, outside the submitted work and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen and Daichii-Sankyo JLMH: reports institutional research grants from PharmaMar, Eisai, Immix BioPharma and Novartis outside the submitted work SS: reports grants and personal fees from Bayer, Lilly and PharmaMar, grants from GlaxoSmithKline, Novartis and Pfizer outside the submitted work BV: reports personal fees from Eisai, Eli Lilly, Novartis, PharmaMar and Abbott; paid testimony for Abbott; and institutional research funding from Eli Lilly, Novartis and PharmaMar, all outside the submitted work JM-B: reports research grants from PharmaMar, Eisai, Immix BioPharma and Novartis outside the submitted work; honoraria for advisory board participation and expert testimony from PharmaMar, Eli Lilly and Company, Bayer and Eisai; and research funding for clinical studies (institutional) from PharmaMar, Eli Lilly and Company, BMS, Pfizer, AROG, Bayer, Eisai, Lixte, Karyopharm, Deciphera, GSK, Novartis, Blueprint, Nektar, Forma, Amgen and Daichii-Sankyo RR, JAMG, GPD and FG: declare that they have no competing interests (© The Author(s), 2022.)
Databáze:	MEDLINE
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