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Clin Cancer Res. 2015 Feb 1;21(3):561-8. doi: 10.1158/1078-0432.CCR-14-1520. Epub 2014 Nov 25.

The high-dose aldesleukin "select" trial: a trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma.

Author information

1
Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts. dmcdermo@bidmc.harvard.edu.
2
Dana-Farber Cancer Institute, Boston, Massachusetts.
3
Brigham and Women's Hospital, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts.
4
University of Washington, Seattle, Washington.
5
Loyola University, Stritch School of Medicine, Chicago, Illinois.
6
Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee.
7
Our Lady Of Mercy Medical Center, New York, New York.
8
Indiana University, Simon Cancer Center, Indianapolis, Indiana.
9
Providence Cancer Center, Earle A. Chiles Research Institute, Portland, Oregon.
10
Dartmouth-Hitchcock Medical Center, Norris Cotton Cancer Center, Dartmouth, New Hampshire.
11
Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
12
Roswell Park Cancer Institute, Buffalo, New York.
13
Lawrence and Memorial Hospital, Waterford, Connecticut.
14
Karmanos Cancer Institute, Detroit, Michigan.
15
Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts.
16
Department of Urology, Mayo Clinic, Rochester, Minnesota.
17
University of California Los Angeles Medical Center, Santa Monica, California.
18
Cedars-Sinai's Samuel Oschin Comprehensive Cancer Institute, West Hollywood, California.
19
Georgetown-Lombardi Cancer Center, Washington, D.C.

Abstract

PURPOSE:

High-dose aldesleukin (HD IL2) received FDA approval for the treatment of metastatic renal cell carcinoma (MRCC) in 1992, producing a 14% objective response rate (ORR) and durable remissions. Retrospective studies suggested that clinical and pathologic features could predict for benefit. The Cytokine Working Group conducted this prospective trial to validate proposed predictive markers of response to HD IL2.

EXPERIMENTAL DESIGN:

Standard HD IL2 was administered to prospectively evaluate whether the ORR of patients with mRCC with "good" predictive pathologic features based on an "integrated selection" model [ISM (e.g., clear-cell histology subclassification and carbonic anhydrase-9 (CA-9) IHC staining] was significantly higher than the ORR of a historical, unselected population. Archived tumor was collected for pathologic analysis including tumor programmed death-ligand 1 (PD-L1) expression.

RESULTS:

One hundred and twenty eligible patients were enrolled between June 11 and September 7; 70% were Memorial Sloan Kettering Cancer Center (New York, NY) intermediate risk, 96% had clear cell RCC, and 99% had prior nephrectomy. The independently assessed ORR was 25% (30/120, 95% CI, 17.5%-33.7%, P = 0.0014; 3 complete responses, 27 partial responses) and was higher than a historical ORR. Thirteen patients (11%) remained progression free at 3 years and the median overall survival was 42.8 months. ORR was not statistically different by ISM classification ("good-risk" 23% vs. "poor-risk" 30%; P = 0.39). ORR was positively associated with tumor PD-L1 expression (P = 0.01) by IHC.

CONCLUSIONS:

In this prospective, biomarker validation study, HD IL2 produced durable remissions and prolonged survival in both "good" and "poor-risk" patients. The proposed ISM was unable to improve the selection criteria. Novel markers (e.g., tumor PD L1 expression) appeared useful, but require independent validation.

PMID:
25424850
PMCID:
PMC4315731
DOI:
10.1158/1078-0432.CCR-14-1520
[Indexed for MEDLINE]
Free PMC Article

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