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

David D. Stenehjem, Michael Toole, Joseph Merriman, Kinjal Parikh, Stephanie Daignault, Sarah Scarlett, Peg Esper, Katherine Skinner, Aaron Udager, Srinivas Kiran Tantravahi, David Gill, Alli M. Straubhar, Archana M. Agarwal, Kenneth F. Grossmann, Wolfram E. Samlowski, Bruce Redman, Neeraj Agarwal, Ajjai Alva

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)941-949
Number of pages9
JournalCancer Immunology, Immunotherapy
Volume65
Issue number8
DOIs
StatePublished - Aug 1 2016

Keywords

  • Clinical benefit
  • High-dose interleukin-2
  • Immunotherapy
  • Metastatic kidney cancer
  • Survival outcomes

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    Stenehjem, D. D., Toole, M., Merriman, J., Parikh, K., Daignault, S., Scarlett, S., Esper, P., Skinner, K., Udager, A., Tantravahi, S. K., Gill, D., Straubhar, A. M., Agarwal, A. M., Grossmann, K. F., Samlowski, W. E., Redman, B., Agarwal, N., & Alva, A. (2016). Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2. Cancer Immunology, Immunotherapy, 65(8), 941-949. https://doi.org/10.1007/s00262-016-1854-1