David D Stenehjem1,2, Michael Toole3,4, Joseph Merriman1, Kinjal Parikh5, Stephanie Daignault3, Sarah Scarlett3, Peg Esper3, Katherine Skinner3, Aaron Udager3, Srinivas Kiran Tantravahi1, David Gill1, Alli M Straubhar1, Archana M Agarwal6, Kenneth F Grossmann1, Wolfram E Samlowski7, Bruce Redman3, Neeraj Agarwal8, Ajjai Alva9. 1. Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA. 2. Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA. 3. University of Michigan, Ann Arbor, MI, USA. 4. Vanderbilt University Medical Center, Nashville, TN, USA. 5. Anderson Cancer Center, Houston, TX, USA. 6. ARUP Laboratories, Department of Pathology, University of Utah, Salt Lake City, UT, USA. 7. Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA. 8. Division of Medical Oncology, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Ste 2123, Salt Lake City, UT, 84112, USA. Neeraj.Agarwal@hci.utah.edu. 9. Comprehensive Cancer Center, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, 48109, USA. ajjai@med.umich.edu.
Abstract
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.
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.
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