Primary anti-VEGF-refractory metastatic renal cell carcinoma (mRCC): Clinical characteristics, risk factors, and subsequent therapy.

Abstract

305 Background: A proportion of patients treated with anti-VEGF therapy first line exhibit progressive disease (PD) as best response (per RECIST). The characteristics and outcome of this population are poorly understood. Methods: Data from patients with mRCC treated with anti-VEGF therapy were collected through the International mRCC Database Consortium from 12 centers. Results: One thousand fifty-six evaluable patients were treated with VEGF-inhibitors as their first-line antiangiogenic therapy. Of those, 272 (26%) patients had PD as best response. Their initial treatment was sunitinib (n=203), sorafenib (n=51), or bevacizumab (n=18). Six percent of patients were favorable risk, 55% intermediate risk, and 39% poor risk as per Heng et al JCO 2009 prognostic factors. On multivariable analysis, predictors of PD at first restaging were KPS < 80% (OR 2.3, p < 0.0001), diagnosis to treatment < 1 year (OR 2.1, p < 0.0001), neutrophilia (OR 1.9, p = 0.0021), thrombocytosis (OR 1.7, p = 0.0068), and anemia (OR 1.6, p = 0.0058). The median progression-free survival (PFS) and overall survival (OS) in patients with primary refractory disease vs. patients without (i.e., partial response or stable disease) was 2.4 vs. 11 months (p<0.0001) and 6.8 vs. 29 months (p<0.0001), respectively. Only 108 (40%) VEGF-refractory patients proceeded to receive 2nd line VEGF inhibitors (sunitinib (n=32), sorafenib (n=44), axitinib (n=2), bevacizumab (n=4)), mTOR inhibitors (temsirolimus (n=14), everolimus (n=11)), or interferon (n=1). The response rate, PFS and OS of this second-line therapy was 9%, 2.5 months and 7.4 months, respectively. The response rate, PFS and OS of those receiving second-line VEGF vs. mTOR inhibitors was 10% vs. 6% (p=NS), 2.8 vs. 2.0 months (p=0.069) and 7.9 vs. 4.7 months (p=0.40), respectively. Conclusions: Primary anti-VEGF-refractory mRCC patients have a dismal prognosis. Second-line anti-mTOR agents may not be better than alternate anti-VEGF agents after primary anti-VEGF failure. Investigation into the mechanism of primary resistance and alternative therapeutic strategies are needed. [Table: see text]