Abstract
Conditional survival (CS) is a clinically useful prediction measure which adjusts a patient’s prognosis based on their duration of survival since initiation of therapy. CS has been described in numerous malignancies, and recently described in patients with metastatic renal cell carcinoma (mRCC) who received vascular endothelial growth factor tyrosine kinase inhibitor (VEGFTKI) therapy. However, CS has been not reported in the context of mRCC treated with high-dose interleukin-2 therapy (HDIL-2). A total of 176 patients with histologically confirmed metastatic clear cell RCC (mccRCC) treated with HDIL-2 at the University of Utah Huntsman Cancer Institute from 1988–2012 were evaluated. Using the Heng/IMDC model, they were stratified by performance status and prognostic risk groups. Two-year CS was defined as the probability of surviving an additional two years from initiation of HDIL-2 to 18 months after the start of HDIL-2 at three-month intervals. The median overall survival (OS) was 19.9 months. Stratifying patients into favourable (n = 35; 20%), intermediate (n = 110; 63%), and poor (n = 31; 18%) prognostic groups resulted in median OS of 47.5 (HR 0.57, 95% CI 0.35–0.88, p = 0.0106 versus intermediate), 19.6 (HR 0.33, 95% CI 0.10–0.33, p < 0.0001 versus poor), and 8.8 (HR 5.34, 95% CI 3.00–9.62, p < 0.0001 versus favourable) months respectively. Two-year overall CS increased from 43% at therapy initiation to 100% at 18 months. These results have significant ramifications in prognostication. Furthermore, it is important when counseling patients with mccRCC who have completed treatment with HDIL-2 and are in active follow-up.
Highlights
Renal cell carcinoma (RCC) is the most common primary renal neoplasm, accounting for over 80% of cases with incidence being 60% more common in men
high-dose interleukin-2 therapy (HDIL-2) was the mainstay of therapy for metastatic renal cell carcinoma (mRCC) until 2005, when large randomised trials revealed that targeted therapies consisting of vascular endothelial growth factor tyrosine kinase inhibitors (VEGFTKIs) and mammalian target of rapamycin inhibitors had improvements in progression free survival (PFS), ORR, and overall survival (OS)
Stratification by Heng/International Metastatic RCC Database Consortium (IMDC) criteria at therapy initiation resulted in OS estimates for the favourable (n = 35; 20%), intermediate (n = 110; 63%), and poor (n = 31; 18%) prognostic groups of 47.5 (HR 0.57, 95% confidence interval (CI) 0.35–0.88, p = 0.0106 versus intermediate), 19.6 (Hazard ratio (HR) 0.33, 95% CI 0.10–0.33, p < 0.0001 versus poor), and 8.8 (HR 5.34, 95% CI 3.00–9.62, p < 0.0001 versus favourable) months respectively
Summary
Renal cell carcinoma (RCC) is the most common primary renal neoplasm, accounting for over 80% of cases with incidence being 60% more common in men. As a subtype of RCC, clear cell (ccRCC) accounts for the vast majority of cases [2]. Approval was based in durable responses seen in a subset of patients (~10%) treated with HDIL-2 [3]. Large retrospective studies recently reported an additional ~30% who do not experience an objective response, but stable disease as the best response [5]. Survival outcomes in these patients achieving stable disease as best response were similar to those achieving partial response as the best response [5,6]. With the emergence of checkpoint inhibition (nivolumab), there has been a resurgence of cancer immunotherapy for mRCC, and an improved appreciation of benefits of immunotherapy in general among oncology providers [7]
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