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. 2016 Aug;65(8):941-9.
doi: 10.1007/s00262-016-1854-1. Epub 2016 Jun 8.

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

David D Stenehjem  1   2 , Michael Toole  3   4 , Joseph Merriman  1 , Kinjal Parikh  5 , Stephanie Daignault  3 , Sarah Scarlett  3 , Peg Esper  3 , Katherine Skinner  3 , Aaron Udager  3 , Srinivas Kiran Tantravahi  1 , David Gill  1 , Alli M Straubhar  1 , Archana M Agarwal  6 , Kenneth F Grossmann  1 , Wolfram E Samlowski  7 , Bruce Redman  3 , Neeraj Agarwal  8 , Ajjai Alva  9
Affiliations

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

David D Stenehjem et al. Cancer Immunol Immunother. 2016 Aug.

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.

Keywords: Clinical benefit; High-dose interleukin-2; Immunotherapy; Metastatic kidney cancer; Survival outcomes.

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Conflict of interest statement

Authors of this paper have nothing to disclose concerning possible financial or personal relationship with commercial entities that may have a direct or indirect interest in the subject of this paper.

Figures

Fig. 1
Fig. 1
Survival outcomes at 2-month landmark a median overall survival stratified by IMDC risk criteria; b PFS and c OS by best response to HDIL-2; and d OS by best response to HDIL-2 in patients who received a VEGFR-TKI or mTORi post-HDIL-2
Fig. 2
Fig. 2
COX proportional hazards model with landmark analysis at 2 months for a PFS and b OS in the entire cohort, and c OS in only those who received VEGFR-TKI or mTORi post-HDIL-2
See this image and copyright information in PMC

References

    1. Hudes GR, Carducci MA, Choueiri TK, et al. NCCN Task force report: optimizing treatment of advanced renal cell carcinoma with molecular targeted therapy. J Natl Compr Cancer Netw. 2011;9(Suppl 1):S1–S29. - PMC - PubMed
    1. Motzer RJ, Hutson TE, Tomczak P, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356:115–124. doi: 10.1056/NEJMoa065044. - DOI - PubMed
    1. Hudes G, Carducci M, Tomczak P, et al. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med. 2007;356:2271–2281. doi: 10.1056/NEJMoa066838. - DOI - PubMed
    1. Sternberg CN, Davis ID, Mardiak J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28:1061–1068. doi: 10.1200/JCO.2009.23.9764. - DOI - PubMed
    1. Escudier B, Pluzanska A, Koralewski P, et al. Bevacizumab plus interferon alfa-2a for treatment of metastatic renal cell carcinoma: a randomised, double-blind phase III trial. Lancet. 2007;370:2103–2111. doi: 10.1016/S0140-6736(07)61904-7. - DOI - PubMed

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