Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials

D. Y.C. Heng, T. K. Choueiri, B. I. Rini, J. Lee, T. Yuasa, S. K. Pal, S. Srinivas, G. A. Bjarnason, J. J. Knox, M. MacKenzie, U. N. Vaishampayan, M. H. Tan, SunYoung Rha, F. Donskov, N. Agarwal, C. Kollmannsberger, S. North, L. A. Wood

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Abstract

Background: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. Patients and Methods: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10 3 /uL, or neutrophil count <1500/mm 3 . Results: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039).When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95%confidence interval 1.378-1.751, P < 0.0001). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

Original languageEnglish
Article numbermdt492
Pages (from-to)149-154
Number of pages6
JournalAnnals of Oncology
Volume25
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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Renal Cell Carcinoma
Clinical Trials
Disease-Free Survival
Databases
Karnofsky Performance Status
Platelet Count
Vascular Endothelial Growth Factor A
Neutrophils
Therapeutics
Confidence Intervals
Calcium
Survival

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

Heng, D. Y. C., Choueiri, T. K., Rini, B. I., Lee, J., Yuasa, T., Pal, S. K., ... Wood, L. A. (2014). Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. Annals of Oncology, 25(1), 149-154. [mdt492]. https://doi.org/10.1093/annonc/mdt492
Heng, D. Y.C. ; Choueiri, T. K. ; Rini, B. I. ; Lee, J. ; Yuasa, T. ; Pal, S. K. ; Srinivas, S. ; Bjarnason, G. A. ; Knox, J. J. ; MacKenzie, M. ; Vaishampayan, U. N. ; Tan, M. H. ; Rha, SunYoung ; Donskov, F. ; Agarwal, N. ; Kollmannsberger, C. ; North, S. ; Wood, L. A. / Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. In: Annals of Oncology. 2014 ; Vol. 25, No. 1. pp. 149-154.
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title = "Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials",
abstract = "Background: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. Patients and Methods: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70{\%}, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10 3 /uL, or neutrophil count <1500/mm 3 . Results: Overall, 768 of 2210 (35{\%}) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22{\%} versus 29{\%} (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039).When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95{\%}confidence interval 1.378-1.751, P < 0.0001). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.",
author = "Heng, {D. Y.C.} and Choueiri, {T. K.} and Rini, {B. I.} and J. Lee and T. Yuasa and Pal, {S. K.} and S. Srinivas and Bjarnason, {G. A.} and Knox, {J. J.} and M. MacKenzie and Vaishampayan, {U. N.} and Tan, {M. H.} and SunYoung Rha and F. Donskov and N. Agarwal and C. Kollmannsberger and S. North and Wood, {L. A.}",
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Heng, DYC, Choueiri, TK, Rini, BI, Lee, J, Yuasa, T, Pal, SK, Srinivas, S, Bjarnason, GA, Knox, JJ, MacKenzie, M, Vaishampayan, UN, Tan, MH, Rha, S, Donskov, F, Agarwal, N, Kollmannsberger, C, North, S & Wood, LA 2014, 'Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials', Annals of Oncology, vol. 25, no. 1, mdt492, pp. 149-154. https://doi.org/10.1093/annonc/mdt492

Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials. / Heng, D. Y.C.; Choueiri, T. K.; Rini, B. I.; Lee, J.; Yuasa, T.; Pal, S. K.; Srinivas, S.; Bjarnason, G. A.; Knox, J. J.; MacKenzie, M.; Vaishampayan, U. N.; Tan, M. H.; Rha, SunYoung; Donskov, F.; Agarwal, N.; Kollmannsberger, C.; North, S.; Wood, L. A.

In: Annals of Oncology, Vol. 25, No. 1, mdt492, 01.01.2014, p. 149-154.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Outcomes of patients with metastatic renal cell carcinoma that do not meet eligibility criteria for clinical trials

AU - Heng, D. Y.C.

AU - Choueiri, T. K.

AU - Rini, B. I.

AU - Lee, J.

AU - Yuasa, T.

AU - Pal, S. K.

AU - Srinivas, S.

AU - Bjarnason, G. A.

AU - Knox, J. J.

AU - MacKenzie, M.

AU - Vaishampayan, U. N.

AU - Tan, M. H.

AU - Rha, SunYoung

AU - Donskov, F.

AU - Agarwal, N.

AU - Kollmannsberger, C.

AU - North, S.

AU - Wood, L. A.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. Patients and Methods: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10 3 /uL, or neutrophil count <1500/mm 3 . Results: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039).When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95%confidence interval 1.378-1.751, P < 0.0001). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

AB - Background: Targeted therapies in metastatic renal cell carcinoma (mRCC) have been approved based on registration clinical trials that have strict eligibility criteria. The clinical outcomes of patients treated with targeted agents but are ineligible for trials are unknown. Patients and Methods: mRCC patients treated with vascular endothelial growth factor-targeted therapy were retrospectively deemed ineligible for clinical trials (according to commonly used inclusion/exclusion criteria) if they had a Karnofsky performance status (KPS) <70%, nonclear-cell histology, brain metastases, hemoglobin ≤9 g/dl, creatinine >2× the upper limit of normal, corrected calcium ≥12 mg/dl, platelet count of <100 × 10 3 /uL, or neutrophil count <1500/mm 3 . Results: Overall, 768 of 2210 (35%) patients in the International Metastatic RCC Database Consortium (IMDC) were deemed ineligible for clinical trials by the above criteria. Between ineligible versus eligible patients, the response rate, median progression-free survival (PFS) and median overall survival of first-line targeted therapy were 22% versus 29% (P = 0.0005), 5.2 versus 8.6 months, and 12.5 versus 28.4 months (both P < 0.0001), respectively. Second-line PFS (if applicable) was 2.8 months in the trial ineligible versus 4.3 months in the trial eligible patients (P = 0.0039).When adjusted by the IMDC prognostic categories, the HR for death between trial ineligible and trial eligible patients was 1.55 (95%confidence interval 1.378-1.751, P < 0.0001). Conclusions: The number of patients that are ineligible for clinical trials is substantial and their outcomes are inferior. Specific trials addressing the unmet needs of protocol ineligible patients are warranted.

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DO - 10.1093/annonc/mdt492

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JF - Annals of Oncology

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