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



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.



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.



Survival benefit with HDIL-2 is achieved in ~50 % patients and extends beyond those achieving objective responses.
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.|Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA.
David D
DD
Stenehjem
University of Michigan, Ann Arbor, MI, USA.|Vanderbilt University Medical Center, Nashville, TN, USA.
Michael
M
Toole
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Joseph
J
Merriman
Anderson Cancer Center, Houston, TX, USA.
Kinjal
K
Parikh
University of Michigan, Ann Arbor, MI, USA.
Stephanie
S
Daignault
University of Michigan, Ann Arbor, MI, USA.
Sarah
S
Scarlett
University of Michigan, Ann Arbor, MI, USA.
Peg
P
Esper
University of Michigan, Ann Arbor, MI, USA.
Katherine
K
Skinner
University of Michigan, Ann Arbor, MI, USA.
Aaron
A
Udager
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Srinivas Kiran
SK
Tantravahi
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
David
D
Gill
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Alli M
AM
Straubhar
ARUP Laboratories, Department of Pathology, University of Utah, Salt Lake City, UT, USA.
Archana M
AM
Agarwal
Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
Kenneth F
KF
Grossmann
Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA.
Wolfram E
WE
Samlowski
University of Michigan, Ann Arbor, MI, USA.
Bruce
B
Redman
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.
Neeraj
N
Agarwal
Comprehensive Cancer Center, Department of Internal Medicine, Division of Hematology/Oncology, University of Michigan, Ann Arbor, MI, 48109, USA. ajjai@med.umich.edu.
Ajjai
A
Alva
D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis
D007376:Interleukin-2
Clinical benefit; High-dose interleukin-2; Immunotherapy; Metastatic kidney cancer; Survival outcomes