832P - C-Myc as a new predictive biomarker for sunitinib in metastatic renal clear cell carcinoma

Date 29 September 2012
Event ESMO Congress 2012
Session Poster presentation I
Topics Renal Cell Cancer
Translational Research
Presenter Pablo Maroto
Authors P. Maroto1, E. Esteban2, E. Fernández-Parra3, M.J. Méndez-Vidal4, M. Domenech5, L. León6, B. Pérez-Valderrama7, V. Calderero8, J.L. Perez Gracia9, F. Algaba10
  • 1Dept. Of Medical Oncology, Hospital de la Sta. Creu i St. Pau, ES-08025 - Barcelona/ES
  • 2Hospital Universitario Central de Asturias, Oviedo/ES
  • 3Medical Oncology, Hospital Nuestra Señora de Valme, Seville/ES
  • 4Medical Oncology, Hospital Reina Sofía, Cordoba/ES
  • 5Oncology, ALthaia, Xarxa Assistencial de Manresa, 08243 - Manresa/ES
  • 6Medical Oncology, Hospital General de Santiago, Santiago de Compostela/ES
  • 7Medical Oncology, Hospital Virgen del Rocío, Seville/ES
  • 8Medical Oncology, Hospital Universitario Miguel Servet, Zaragoza/ES
  • 9Clinical Oncology, Clinica Universitaria de Navarra, 31008 - Pamplona/ES
  • 10Medical Oncology, Fundación Puigvert, Barcelona/ES

Abstract

Background

Sunitinib is a tyrosin kinase inhibitor with proven efficacy in renal clear cell carcinoma (RCC). However we still lack properly validated molecular predictors of response. Two subtypes of sporadic VHL-deficient RCC were proposed based on HIF1α and HIF2α expression and c-Myc activation. This molecular subclassification could provide a framework for current targeted therapies. This study aims to explore the predictive value of this molecular signature.

Methods

An observational prospective study involving 10 Spanish Hospitals was designed to collect formalin-fixed paraffin-embedded primary tumor tissue samples. We enrolled consecutively attending adults who had a centralized pathologically confirmed diagnosis of RCC with a clear-cell histology and advanced disease. Eligible patients were treatment naive and scheduled for sunitinib following routine clinical practice. The protocol was approved by the medical ethics committee of all participating institutions, and signed informed consent was obtained for all patients. Selected biomarkers were analyzed by immunohistochemistry following established protocols.

Results

From March 2009 to February 2011, 80 patients were included. At the time of the analysis, tumor samples were available for 64 patients and 58 were evaluable for c-Myc expression. Only 33% (19/58) showed c-Myc immunostainig (any score: 1–3) and 67% (39/58) were negative for c-Myc expression (scored as 0). Both groups were well balanced and non significant differences in risk prognostic factors were found. Regarding Sunitinib efficacy, significant differences in PFS were found between both molecular subgroups. A median PFS of 5.4 months was found in patients with c-Myc positive primary tumors vs. 11.4 months in patients with c-Myc negative primary tumors (HR = 2.54, 95%CI (1.28, 5.07), p = 0.0062). Correlation of c-Myc expression with other related biomarkers is underway.

Conclusions

Although, this is a small sample and validation is still needed, these results suggest a promising value for c-Myc immunostaining as a novel tool to identify those patients with RCC with more probabilities of obtaining benefit with Sunitinib through an accessible and reproducible technique.

This study was supported by an Independent Investigator Research grant from Pfizer Inc.

Disclosure

P. Maroto: Compensation of consultant/Advisory role at Pfizer.

E. Esteban: Compensation of consultant/Advisory role at Pfizer.

All other authors have declared no conflicts of interest.