Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2.

PURPOSE: In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16-20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e., to those who achieve stable disease as the best response to treatment. MATERIALS AND METHODS: All sequential treatment naïve mRCC patients treated with HDIL-2 at the University of Utah (1988-2013) and University of Michigan (1997-2013) were included. Best responses on treatment were associated with survival outcomes using log-rank and COX regression with a landmark analysis at 2 months. RESULTS: 391 patients (75 % male; median age 55 years) were included and belonged to the following prognostic risk categories: 20 % good, 64 % intermediate, and 15 % poor. Best responses on treatment were complete response (9 %), partial response (10 %), stable disease (32 %), progressive disease (42 %), and not evaluable for response (7 %). No significant differences in progression-free survival (HR 0.74, 95 % CI 0.48-1.1, p = 0.14) or overall survival (HR 0.66, 95 % CI 0.39-1.09, p = 0.11) were observed between patients achieving partial response versus stable disease. Significant differences in progression-free survival (HR 0.13, 95 % CI 0.09-0.22, p < 0.0001) and overall survival (HR 0.33, 95 % CI 0.23-0.48, p < 0.0001) were observed between patients achieving stable disease compared to those with progressive disease and who were not evaluable. CONCLUSIONS: Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses.

Conditional survival of metastatic renal cell carcinoma patients treated with high-dose interleukin-2.

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.