Evidence and Clinical Relevance of Tumor Flare in Patients Who Discontinue Tyrosine Kinase Inhibitors for Treatment of Metastatic Renal Cell Carcinoma

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Iacovelli R., Massari F., Albiges L., Loriot Y., Massard C., Fizazi K., Escudier B.

European Urology 2014

Background: Several tyrosine kinase inhibitors (TKIs) and one monoclonal antibody targeting the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) axis have been approved for the treatment of metastatic renal cell carcinoma (mRCC). Preclinical data suggest that cessation of anti-VEGF therapy may generate a tumor flare (TF) but its clinical relevance is still questionable. Objective: This analysis investigates the occurrence of tumor flare and its prognostic role after discontinuation of anti-VEGFR TKIs in patients affected by mRCC. Design, setting, and participants: Patients with mRCC treated with first-line sunitinib or pazopanib at standard dosages were screened. Patients included in the analysis were required to have: (1) discontinued treatment because of progression of disease or intolerable toxicity or sustained response; (2) evaluation of tumor growth rates immediately before (GR1) and after discontinuation (GR2); and (3) no treatment during evaluation of GR2. Outcome measurements and statistical analysis: Overall survival (OS) was the main outcome. TF was calculated as the difference between the GR values (TF = GR2 – GR1). Cox proportional hazards regression was used to assess the prognostic role. Results and limitations: Sixty-three consecutive patients were analyzed; the median duration of treatment was 9.3 mo, the median progression-free survival (PFS) was 11.1 mo, and the median OS was 41.5 mo. The reasons for treatment discontinuation were sustained response (partial response/stable disease) in 15.9%, toxicity in 22.2%, and progression of disease in 61.9% of cases. The median GR1 and GR2 were 0.16. cm/mo (interquartile range [IQR] -0.07 to 0.53) and…(vermás)


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