Failure of initial VEGF-targeted therapy in metastatic renal cell carcinoma (mRCC): What next?

5098 Background: The characterization and efficacy of second-line targeted therapy in patients with metastatic RCC who failed first-line VEGF-targeted therapy in a population-based setting is of clinical relevance but remains to be assessed. Methods: Provincial registries and clinical databases from seven cancer centers (3 in US and 4 in Canada) identified patients with mRCC who received first-line anti-VEGF targeted therapy between 2005–2007. Patient characteristics, data on second-line therapy and outcomes were analyzed. Results: 645 patients with mRCC who received initial VEGF-targeted therapy were identified (sunitinib, sorafenib or bevacizumab) and had a median follow-up of 25 mos. Of these, 218 patients (34%) received second-line targeted therapy: the median age was 62 yrs (range, 41–87), median KPS was 90%, 90% had prior nephrectomy, 3.8% had non-clear cell histology, 5.8% had brain metastases and 79% had > 1 metastatic site. Second-line therapy included anti-VEGF agents (sunitinib n = 93, sorafenib n = 80, bevacizumab n = 11, axitinib n = 8) and mTOR-inhibiting agents (temsirolimus n = 21, everolimus n = 3). Patient characteristics were similar aside from more non-clear cell histology in patients receiving second-line mTOR-inhibiting agents (14% vs 3% p = 0.045). On multivariable analysis, only a higher baseline KPS score prior to first-line therapy predicted which patients were more likely to receive second-line therapy (p < 0.0001). The median time to treatment failure (TTF) of second-line therapy was 4.9 mos for anti-VEGF therapy and 2.5 mos for mTOR inhibitors (p = 0.014). After adjusting for MSKCC prognostic profile (favorable, intermediate, poor), the hazard ratio for TTF was 0.52 (95%CI:0.29–0.91) in pts receiving anti-VEGF therapy. Overall survival from start of second-line therapy was not different between anti-VEGF or anti-mTOR drugs (14.2 vs 10.6 respectively; p = 0.38). 70 patients (10%) received third-line therapy. Conclusions: Baseline KPS is an independent predictor of receiving second-line targeted therapy. Patients who receive a second-line anti-VEGF drug appear to have a longer TTF than those who receive a second-line anti-mTOR drug. However, patient selection may account for this finding and overall survival was not significantly different. Results of ongoing randomized trials are awaited. [Table: see text]

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