<scp>TP53</scp> mutations and survival in ovarian carcinoma patients receiving first‐line chemotherapy plus bevacizumab: Results of the <scp>MITO16A</scp>/<scp>MaNGO OV</scp>‐2 study

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.

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Journal
International Journal of Cancer
Published
2024-10-16
DOI
https://doi.org/10.1002/ijc.35203
Citations
2
Primary Topic
Ovarian cancer diagnosis and treatment
Type
article
Field-Weighted Citation Impact
1.07

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article

TP53 mutations and survival in ovarian carcinoma patients receiving first‐line chemotherapy plus bevacizumab: Results of the MITO16A/MaNGO OV‐2 study

Mattia Bugatti, Lara Paracchini, Laura Arenare, Elisabetta Kuhn et al.
2 citations
International Journal of Cancer
Ovarian cancer diagnosis and treatment
1.07
article

TP53 mutations and survival in ovarian carcinoma patients receiving first‐line chemotherapy plus bevacizumab: Results of the MITO16A/MaNGO OV‐2 study

Mattia Bugatti, Lara Paracchini, Laura Arenare, Elisabetta Kuhn, Laura Ardighieri, Luca Beltrame, Daniela Califano, Germana Tognon, Sabrina Chiara Cecere, Vittorio Simeon, Paolo Chiodini, Giosuè Scognamiglio, Eliana Bignotti, Maurizio D’Incalci, Franco Odicino, Domenica Lorusso, Anna Spina, Sergio Marchini, Enrico Sartori, Daniela Russo, Sandro Pignata, Francesco Perrone, Andrea De Censi
article en
2 citations

Abstract

To date, there are no biomarkers that define a patient subpopulation responsive to bevacizumab (BEV), an effective treatment option for advanced ovarian carcinoma (OC). In the context of the MITO16A/MaNGO OV-2 trial, a Phase IV study of chemotherapy combined with BEV in first-line treatment of advanced OC, we evaluated TP53 mutations by next-generation sequencing and p53 expression by immunohistochemistry (IHC) on 202 and 311 cases, respectively. We further correlated TP53 mutations in terms of type, function, and site, and IHC data with patients' clinicopathological characteristics and survival. TP53 missense mutations of unknown function (named unclassified) represented the majority of variants in our population (44.4%) and were associated with a significantly improved overall survival (OS) both in univariable (hazard ratio [HR] = 0.43, 95% confidence interval [CI] = 0.20-0.92, p = .03) and multivariable analysis (HR = 0.39, 95% CI = 0.18-0.86, p = .02). Concordance between TP53 mutational analysis and IHC was 91%. We observed an HR of 0.70 for OS in patients with p53 IHC overexpression compared to p53 wild-type, which however did not reach statistical significance (p = .31, 95% CI = 0.36-1.38). Our results indicate that the presence of unclassified TP53 mutations has favorable prognostic significance in patients with OC receiving upfront BEV plus chemotherapy. In particular, unclassified missense TP53 mutations characterize a subpopulation of patients with a significant survival advantage, independently of clinicopathological characteristics. Our findings warrant future investigations to confirm the prognostic impact of TP53 mutations in BEV-treated OC patients and deserve to be assessed for their potential predictive role in future randomized clinical studies.

International Journal of CancerVol. 156(5)
University of Milan (IT), University of Campania "Luigi Vanvitelli" (IT), Agostino Gemelli University Polyclinic (IT), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Ente Ospedaliero Ospedali Galliera (IT), Ospedale Maggiore (IT), Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia (IT), Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Fondazione IRCCS Istituto Nazionale dei Tumori (IT), IRCCS Humanitas Research Hospital (IT), University of Brescia (IT)
Ministero della Salute
Good health and well-being
Openalex Percentile: Top 20%
Ovarian cancer diagnosis and treatment
1.07
DOIOpen Access PDFOpenAlex
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