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Phase II trial of bevacizumab and erlotinib in patients with metastatic renal carcinoma (RCC)

English

Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 5 de junio del 2004

This presentation discusses off-label use of bevacizumab for RCC.  It also discusses the use of erlotinib for the treatment of RCC which has not been approved by the FDA.

Presenter: J.D. Hainsworth
Presenter's Affiliation: Sarah Cannon Cancer Center/Tennessee Oncology, Nashville, TN
Type of Session: Scientific

Background

The incidence of renal cell carcinoma (RCC) is increasing with aproximately 30,000 new cases expected this year.  The median survival of patients with metastatic renal cell carcinoma is approximately one year and only 10% of patients survive more than 2 years.  High-dose IL-2 and IFN-a produce responses in a minority of patients.  One of the most common genetic abnormalities in RCC is loss of the VHL protein which results in activation of HIFa and factors regulated by HIFa such as VEGF, PDGF, TGF, and EGF.  The rationale of this study rests on the hypothesis that combined VEGF and EGFR inhibition would result in more effective treatment.  Also, bevacizumab, an anti-VEGF antibody, has shown to prolong time to tumor progression (TTP) in second-line therapy of advanced RCC versus placebo. 

Materials and Methods

62 patients with metastatic RCC who had failed 0 or 1 previous systemic regimens were entered to the study between 2/2003 and 1/2004

The median age was 61 and there were 50 males and 12 females

Most patients did not received prior chemotherapy treatment

All patients had prior nephrectomy

Most common sites of metastases: lung, liver, bones, lymph-nodes and adrenals

Motzer risk category: 26 patients (42%) low risk; 20 (32%) intermediate risk; 16 (26%) high 

Results

Author's Conclusions

Clinical/Scientific Implications
The study reports the results of a phase II clinical trial of a combination of two targeted agents, the monoclonal antibody targeting VEGF,bevacizumab, and the tyrosine kinase inhibitor, erlotinib.  Our understanding of the multiple genetic abnormalities and alterations of different biochemical pathways underlying the development of tumors has resulted in the discovery of novel agents targeting specific pathways.  Results of clinical trials with these agents as monotherapy have shown modest clinical activity in RCC.  The regimen bevacizumab/erlotinib has demonstrated substantial activity in this disease supporting the hypothesis that combining agents targeting multiple biochemical pathways results in more effective treatment.  It would be important to identify the patient population that will benefit from this or similar therapy and to predict early during treatment which patients will progress.  Efforts to define markers of response in subsequent trials are necessary.  Further study of this combination approach is warranted.

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