Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma.

Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months.

Initial patterns of care with oral targeted therapies for patients with renal cell carcinoma.

OBJECTIVES: To characterize the contemporary use of oral-targeted therapies (ie, sunitinib, sorafenib) among patients with renal cell carcinoma (RCC) and to assess the factors associated with short-term and sequential treatment. METHODS: We used an administrative claims database of privately insured patients to evaluate oral-targeted therapy use among patients with RCC from 2006 to 2007. After identifying patients with RCC who had received sunitinib and/or sorafenib, we determined the prevalence of patients treated with short-term and/or sequential therapy. We performed bivariate and multivariate analyses to estimate the associations between the patient characteristics and receipt of short-term and/or sequential treatment regimens. RESULTS: We identified 938 patients with RCC who had initially been treated with sunitinib (n = 554) or sorafenib (n = 384). In this group, 36% and 23% of patients had received short-term or sequential therapy, respectively. Most patients (61%) who had received sequential therapy had undergone short-term treatment with ≥1 drugs, with second-line sorafenib more likely to be given as short-term therapy than sunitinib (63% vs 34%, P < .001). Short-term therapy was more common in female patients (odds ratio 1.53, 95% confidence interval 1.12-2.09) and patients in the Southern United States (odds ratio 1.71, 95% confidence interval 1.05-2.80). Sequential therapy was more common among patients receiving sorafenib first (odds ratio 2.30, 95% confidence interval 1.64-3.21). CONCLUSIONS: Short-term and sequential oral targeted therapy use was relatively prevalent among patients with RCC. For patients treated with sunitinib and sorafenib, the patterns of short-term use varied by the sequence of medications, suggesting differences in the effectiveness or tolerability of each regimen. These findings highlight the need for future studies to characterize the "real-world" clinical outcomes and economic effect associated with these treatment courses.