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
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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