Molecular Subtypes of Clear Cell Renal Cell Carcinoma Are Associated With Outcome During Pazopanib Therapy in the Metastatic Setting
Autor: | Annelies Verbiest, Nathalie Rioux-Leclercq, Benoit Beuselinck, Steven Joniau, Aurélien de Reyniès, Laure Caruana, Brigitte Laguerre, Kathleen Van den Eynde, Gabrielle Couchy, Hendrik Van Poppel, Jessica Zucman-Rossi, Evelyne Lerut, Agnieszka Wozniak, Sylvie Job, Raymond Oyen |
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Přispěvatelé: | Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Génomique Fonctionnelle des Tumeurs Solides (U1162), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, University Hospitals Leuven [Leuven], Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Ligue Nationale Contre le Cancer (LNCC), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ) |
Rok vydání: | 2018 |
Předmět: |
Male
0301 basic medicine Oncology medicine.medical_specialty Indazoles Urology [SDV.CAN]Life Sciences [q-bio]/Cancer Predictive Pazopanib 03 medical and health sciences 0302 clinical medicine Molecular classification Renal cell carcinoma Internal medicine Biomarkers Tumor Humans Medicine Prospective Studies Neoplasm Metastasis Carcinoma Renal Cell Vascular endothelial growth factor receptor tyrosine kinase inhibitor Aged Retrospective Studies Aged 80 and over Sulfonamides Univariate analysis Tumor size business.industry Sunitinib Biomarker Middle Aged medicine.disease Kidney Neoplasms Progression-Free Survival Gene expression profiling 3. Good health Clear cell renal cell carcinoma Pyrimidines Treatment Outcome 030104 developmental biology 030220 oncology & carcinogenesis Biomarker (medicine) Female business medicine.drug |
Zdroj: | Clinical Genitourinary Cancer Clinical Genitourinary Cancer, Elsevier, 2018, 16 (3), pp.e605-e612. ⟨10.1016/j.clgc.2017.10.017⟩ Clinical Genitourinary Cancer, 2018, 16 (3), pp.e605-e612. ⟨10.1016/j.clgc.2017.10.017⟩ |
ISSN: | 1558-7673 |
Popis: | International audience; Background: We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment.Patients and methods: We classified 28 mccRCC tumors treated with pazopanib as first-line therapy, as described previously. The primary endpoints were PFS and OS from the start of pazopanib. A secondary endpoint was ORR. Because there were only 2 ccrcc3 tumors, they were pooled with the ccrcc2 tumors for outcome analysis.Results: PFS was 9 months for the ccrcc2 and ccrcc3 tumors, 5 months for ccrcc1 tumors, and 3 months for the ccrcc4 tumors (P = .011). The corresponding OS duration was 69, 19, and 5 months (P = .003). The corresponding ORR was 50%, 33%, and 0%. The corresponding mean tumor size decreased by 34%, 6%, and 2% (P = .032). The ccrcc1-4 classification was a stronger predictor of outcome than the International Metastatic Renal Cell Carcinoma Database Consortium score on univariate analysis (P = .011 vs. P = .094 for PFS and P = .003 vs. .013 for OS). Both remained independent on bivariate analysis.Conclusion: The molecular subtypes of mccRCC are associated with outcome on pazopanib as first-line therapy. The prognostic and predictive value of the ccrcc1-4 molecular classification requires validation in prospective trials. |
Databáze: | OpenAIRE |
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