TY - JOUR
T1 - The high-dose aldesleukin "select" trial
T2 - A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma
AU - McDermott, David F.
AU - Cheng, Su Chun
AU - Signoretti, Sabina
AU - Margolin, Kim A.
AU - Clark, Joseph I.
AU - Sosman, Jeffrey A.
AU - Dutcher, Janice P.
AU - Logan, Theodore F.
AU - Curti, Brendan D.
AU - Ernstoff, Marc S.
AU - Appleman, Leonard
AU - Wong, Michael K.K.
AU - Khushalani, Nikhil I.
AU - Oleksowicz, Leslie
AU - Vaishampayan, Ulka N.
AU - Mier, James W.
AU - Panka, David J.
AU - Bhatt, Rupal S.
AU - Bailey, Alexandra S.
AU - Leibovich, Bradley C.
AU - Kwon, Eugene D.
AU - Kabbinavar, Fairooz F.
AU - Belldegrun, Arie S.
AU - Figlin, Robert A.
AU - Pantuck, Allan J.
AU - Regan, Meredith M.
AU - Atkins, Michael B.
N1 - Publisher Copyright:
©2014 AACR.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-14-1520
DO - 10.1158/1078-0432.CCR-14-1520
M3 - Article
C2 - 25424850
AN - SCOPUS:84961289871
SN - 1078-0432
VL - 21
SP - 561
EP - 568
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 3
ER -