Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy

A population-based study

Lauren C. Harshman, Wanling Xie, Georg A. Bjarnason, Jennifer J. Knox, Mary MacKenzie, Lori Wood, Sandy Srinivas, Ulka N. Vaishampayan, Min Han Tan, SunYoung Rha, Frede Donskov, Neeraj Agarwal, Christian Kollmannsberger, Scott North, Brian I. Rini, Daniel Y.C. Heng, Toni K. Choueiri

Research output: Contribution to journalArticle

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Abstract

Background: The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival-a measure that accounts for elapsed time since treatment initiation-for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies. Methods: We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival. Findings: In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0-34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to 51% (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to 68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11% (8-15) to 73% (43-89) in the poor risk group. Interpretation: Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.

Original languageEnglish
Pages (from-to)927-935
Number of pages9
JournalThe Lancet Oncology
Volume13
Issue number9
DOIs
Publication statusPublished - 2012 Sep 1

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Renal Cell Carcinoma
Vascular Endothelial Growth Factor A
Survival
Population
Therapeutics
Republic of Korea
Singapore
Denmark
Canada
Histology
Databases

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Harshman, L. C., Xie, W., Bjarnason, G. A., Knox, J. J., MacKenzie, M., Wood, L., ... Choueiri, T. K. (2012). Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: A population-based study. The Lancet Oncology, 13(9), 927-935. https://doi.org/10.1016/S1470-2045(12)70285-1
Harshman, Lauren C. ; Xie, Wanling ; Bjarnason, Georg A. ; Knox, Jennifer J. ; MacKenzie, Mary ; Wood, Lori ; Srinivas, Sandy ; Vaishampayan, Ulka N. ; Tan, Min Han ; Rha, SunYoung ; Donskov, Frede ; Agarwal, Neeraj ; Kollmannsberger, Christian ; North, Scott ; Rini, Brian I. ; Heng, Daniel Y.C. ; Choueiri, Toni K. / Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy : A population-based study. In: The Lancet Oncology. 2012 ; Vol. 13, No. 9. pp. 927-935.
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title = "Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: A population-based study",
abstract = "Background: The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival-a measure that accounts for elapsed time since treatment initiation-for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies. Methods: We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival. Findings: In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0-34·4). We recorded an increase in the 2-year conditional survival probability from 44{\%} (95{\%} CI 41-47) at 0 months to 51{\%} (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11{\%} (8-15) at 0 months to 33{\%} (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44{\%} (41-47) to 68{\%} (60-75) in the overall population and from 74{\%} (68-79) to 90{\%} (77-96) in the favourable group, 49{\%} (45-53) to 57{\%} (45-67) in the intermediate group, and 11{\%} (8-15) to 73{\%} (43-89) in the poor risk group. Interpretation: Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.",
author = "Harshman, {Lauren C.} and Wanling Xie and Bjarnason, {Georg A.} and Knox, {Jennifer J.} and Mary MacKenzie and Lori Wood and Sandy Srinivas and Vaishampayan, {Ulka N.} and Tan, {Min Han} and SunYoung Rha and Frede Donskov and Neeraj Agarwal and Christian Kollmannsberger and Scott North and Rini, {Brian I.} and Heng, {Daniel Y.C.} and Choueiri, {Toni K.}",
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Harshman, LC, Xie, W, Bjarnason, GA, Knox, JJ, MacKenzie, M, Wood, L, Srinivas, S, Vaishampayan, UN, Tan, MH, Rha, S, Donskov, F, Agarwal, N, Kollmannsberger, C, North, S, Rini, BI, Heng, DYC & Choueiri, TK 2012, 'Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy: A population-based study', The Lancet Oncology, vol. 13, no. 9, pp. 927-935. https://doi.org/10.1016/S1470-2045(12)70285-1

Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy : A population-based study. / Harshman, Lauren C.; Xie, Wanling; Bjarnason, Georg A.; Knox, Jennifer J.; MacKenzie, Mary; Wood, Lori; Srinivas, Sandy; Vaishampayan, Ulka N.; Tan, Min Han; Rha, SunYoung; Donskov, Frede; Agarwal, Neeraj; Kollmannsberger, Christian; North, Scott; Rini, Brian I.; Heng, Daniel Y.C.; Choueiri, Toni K.

In: The Lancet Oncology, Vol. 13, No. 9, 01.09.2012, p. 927-935.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Conditional survival of patients with metastatic renal-cell carcinoma treated with VEGF-targeted therapy

T2 - A population-based study

AU - Harshman, Lauren C.

AU - Xie, Wanling

AU - Bjarnason, Georg A.

AU - Knox, Jennifer J.

AU - MacKenzie, Mary

AU - Wood, Lori

AU - Srinivas, Sandy

AU - Vaishampayan, Ulka N.

AU - Tan, Min Han

AU - Rha, SunYoung

AU - Donskov, Frede

AU - Agarwal, Neeraj

AU - Kollmannsberger, Christian

AU - North, Scott

AU - Rini, Brian I.

AU - Heng, Daniel Y.C.

AU - Choueiri, Toni K.

PY - 2012/9/1

Y1 - 2012/9/1

N2 - Background: The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival-a measure that accounts for elapsed time since treatment initiation-for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies. Methods: We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival. Findings: In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0-34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to 51% (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to 68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11% (8-15) to 73% (43-89) in the poor risk group. Interpretation: Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.

AB - Background: The advent of targeted therapies in the past 7 years has extended median survival for metastatic renal-cell carcinoma. This improvement in clinical outcome has created a need for new, more accurate prognostic measures. We assessed the use of conditional survival-a measure that accounts for elapsed time since treatment initiation-for prognostication in patients with metastatic renal-cell carcinoma treated with first-line VEGF-targeted therapies. Methods: We obtained data for patients with metastatic renal-cell carcinoma who were treated with a first-line VEGF-targeted therapy between April 7, 2003, and Oct 12, 2010, from our large multi-institutional International mRCC Database Consortium (centres in Canada, the USA, Singapore, Denmark, and South Korea). All histologies, performance statuses, and prognostic risk groups were included. The primary outcome was 2-year conditional survival, defined as the probability of surviving an additional 2 years from a given timepoint since the start of targeted therapy. Secondary analyses included 1-year and 3-year conditional survival, along with stratification of patients by Heng prognostic risk criteria and Karnofsky performance score, and conditional survival based on length of time on therapy. We used the Kaplan-Meier method and a landmark analysis to calculate conditional survival. Findings: In the 1673 patients analysed, median follow-up for alive patients was 20·1 months (IQR 9·0-34·4). We recorded an increase in the 2-year conditional survival probability from 44% (95% CI 41-47) at 0 months to 51% (46-55) at 18 months since beginning targeted therapy. When stratified by the Heng prognostic risk criteria defined at therapy initiation, 2-year conditional survival changed little in the favourable and intermediate groups, but in the poor-risk group, 2-year conditional survival improved from 11% (8-15) at 0 months to 33% (18-48) after 18 months. When conditioned on time on targeted therapy from 0 months to 18 months, 2-year conditional survival improved from 44% (41-47) to 68% (60-75) in the overall population and from 74% (68-79) to 90% (77-96) in the favourable group, 49% (45-53) to 57% (45-67) in the intermediate group, and 11% (8-15) to 73% (43-89) in the poor risk group. Interpretation: Conditional survival is a clinically useful prediction measure that adjusts prognosis of patients with metastatic renal-cell carcinoma on the basis of survival since treatment initiation or therapy duration. Conditional survival might be especially relevant to adjust prognosis for poor-risk patients.

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