TY - JOUR
T1 - Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2
AU - Stenehjem, David D.
AU - Toole, Michael
AU - Merriman, Joseph
AU - Parikh, Kinjal
AU - Daignault, Stephanie
AU - Scarlett, Sarah
AU - Esper, Peg
AU - Skinner, Katherine
AU - Udager, Aaron
AU - Tantravahi, Srinivas Kiran
AU - Gill, David
AU - Straubhar, Alli M.
AU - Agarwal, Archana M.
AU - Grossmann, Kenneth F.
AU - Samlowski, Wolfram E.
AU - Redman, Bruce
AU - Agarwal, Neeraj
AU - Alva, Ajjai
N1 - Publisher Copyright:
© 2016, Springer-Verlag Berlin Heidelberg.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Clinical benefit
KW - High-dose interleukin-2
KW - Immunotherapy
KW - Metastatic kidney cancer
KW - Survival outcomes
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U2 - 10.1007/s00262-016-1854-1
DO - 10.1007/s00262-016-1854-1
M3 - Article
C2 - 27277816
AN - SCOPUS:84976320996
VL - 65
SP - 941
EP - 949
JO - Cancer Immunology and Immunotherapy
JF - Cancer Immunology and Immunotherapy
SN - 0340-7004
IS - 8
ER -