Von Hippel-Lindau gene mutation status is associated with a dichotomous response in primary and metastatic tumors in patients receiving bevacizumab and erlotinib for metastatic renal cell carcinoma

Abstract

15522 Background: A single arm phase II study is underway evaluating the safety and clinical benefit of presurgical bevacizumab and erlotinib in the management of patients with untreated conventional renal cell carcinoma (RCC). It is not known how the presence or absence of von Hippel Lindau (VHL) mutations affect the response to therapy in the primary or metastatic site, and whether VHL mutational status is predictive for either. Methods: Patients enrolled had conventional RCC, measurable metastatic disease, a primary tumor in place, no prior systemic therapy, a PS of 0 or 1 and no brain metastases. A total of 35 patients were enrolled as of January 8, 2007. Patients were treated with bevacizumab for 4 cycles and erlotinib for 8 weeks, and underwent cytoreductive nephrectomy at week 10 (4 weeks after the last dose of bevacizumab). A VHL gene mutation and methylation analysis was completed on nephrectomy specimens from the first 18 evaluable patients. Patients were grouped according to the presence or absence of functional VHL gene inactivation (mutation and/or methylation). Two-sample T-test and Fisher’s exact test were performed. Results: Ten patients (55%) demonstrated either VHL mutation or methylation ( table 1 ). Patients with no VHL gene inactivation demonstrated more robust primary tumor shrinkage, but did not demonstrate partial responses (PRs). Table 1 . Conclusions: These findings, although preliminary, suggest a dichotomous response in the primary and metastatic disease sites according to VHL functional status. Ongoing evaluation of new treatment strategies using antivascular/targeted agents in RCC may benefit from molecular stratification. [Table: see text] No significant financial relationships to disclose.