The high-dose aldesleukin "select" trial

A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma

David F. McDermott, Su Chun Cheng, Sabina Signoretti, Kim A. Margolin, Joseph I. Clark, Jeffrey A. Sosman, Janice P. Dutcher, Theodore Logan, Brendan D. Curti, Marc S. Ernstoff, Leonard Appleman, Michael K K Wong, Nikhil I. Khushalani, Leslie Oleksowicz, Ulka N. Vaishampayan, James W. Mier, David J. Panka, Rupal S. Bhatt, Alexandra S. Bailey, Bradley C. Leibovich & 7 others Eugene D. Kwon, Fairooz F. Kabbinavar, Arie S. Belldegrun, Robert A. Figlin, Allan J. Pantuck, Meredith M. Regan, Michael B. Atkins

Research output: Contribution to journalArticle

71 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)561-568
Number of pages8
JournalClinical Cancer Research
Volume21
Issue number3
DOIs
StatePublished - Feb 1 2015

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Renal Cell Carcinoma
Interleukin-2
Neoplasms
Ligands
Survival
Validation Studies
Therapeutics
Tumor Biomarkers
Nephrectomy
Patient Selection
Histology
Research Design
Retrospective Studies
Biomarkers
Staining and Labeling
Cytokines
aldesleukin
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

The high-dose aldesleukin "select" trial : A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. / McDermott, David F.; Cheng, Su Chun; Signoretti, Sabina; Margolin, Kim A.; Clark, Joseph I.; Sosman, Jeffrey A.; Dutcher, Janice P.; Logan, Theodore; Curti, Brendan D.; Ernstoff, Marc S.; Appleman, Leonard; Wong, Michael K K; Khushalani, Nikhil I.; Oleksowicz, Leslie; Vaishampayan, Ulka N.; Mier, James W.; Panka, David J.; Bhatt, Rupal S.; Bailey, Alexandra S.; Leibovich, Bradley C.; Kwon, Eugene D.; Kabbinavar, Fairooz F.; Belldegrun, Arie S.; Figlin, Robert A.; Pantuck, Allan J.; Regan, Meredith M.; Atkins, Michael B.

In: Clinical Cancer Research, Vol. 21, No. 3, 01.02.2015, p. 561-568.

Research output: Contribution to journalArticle

McDermott, DF, Cheng, SC, Signoretti, S, Margolin, KA, Clark, JI, Sosman, JA, Dutcher, JP, Logan, T, Curti, BD, Ernstoff, MS, Appleman, L, Wong, MKK, Khushalani, NI, Oleksowicz, L, Vaishampayan, UN, Mier, JW, Panka, DJ, Bhatt, RS, Bailey, AS, Leibovich, BC, Kwon, ED, Kabbinavar, FF, Belldegrun, AS, Figlin, RA, Pantuck, AJ, Regan, MM & Atkins, MB 2015, 'The high-dose aldesleukin "select" trial: A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma', Clinical Cancer Research, vol. 21, no. 3, pp. 561-568. https://doi.org/10.1158/1078-0432.CCR-14-1520
McDermott, David F. ; Cheng, Su Chun ; Signoretti, Sabina ; Margolin, Kim A. ; Clark, Joseph I. ; Sosman, Jeffrey A. ; Dutcher, Janice P. ; Logan, Theodore ; Curti, Brendan D. ; Ernstoff, Marc S. ; Appleman, Leonard ; Wong, Michael K K ; Khushalani, Nikhil I. ; Oleksowicz, Leslie ; Vaishampayan, Ulka N. ; Mier, James W. ; Panka, David J. ; Bhatt, Rupal S. ; Bailey, Alexandra S. ; Leibovich, Bradley C. ; Kwon, Eugene D. ; Kabbinavar, Fairooz F. ; Belldegrun, Arie S. ; Figlin, Robert A. ; Pantuck, Allan J. ; Regan, Meredith M. ; Atkins, Michael B. / The high-dose aldesleukin "select" trial : A trial to prospectively validate predictive models of response to treatment in patients with metastatic renal cell carcinoma. In: Clinical Cancer Research. 2015 ; Vol. 21, No. 3. pp. 561-568.
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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.",
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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

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.

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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