Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors: a single institution experience

Marc R. Matrana, Tharakeswara Bathala, Matthew T. Campbell, Cihan Duran, Aditya Shetty, Purnima Teegavarapu, Sarathi Kalra, Lianchun Xiao, Bradley Atkinson, Paul Corn, Eric Jonasch, Nizar M. Tannir

Research output: Contribution to journalArticle

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Abstract

Objective: To explore the efficacy and safety of pazopanib in a ‘real-world’ setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited. Patients and Methods: We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables. Results: In all, 88 patients were identified; 74 were evaluable for response: two (3%) had a complete response, 27 (36%) a partial response, 36 (49%) had stable disease and nine (12%) had progressive disease. The median PFS was 13.7 months [95% confidence interval (CI) 8.7–18.3]. PFS was correlated with a Karnofsky Performance Status score of <80 [hazard ratio (HR) 3.26, P < 0.001] and serum lactate dehydrogenase of >1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95% CI 20.2–not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95% CI 3.3–25.7) with VEGFR-TKI and 5 months (95% CI 3.5–15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95% CI 12.9–not reached) and 14.2 months (95% CI 8.1–not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37). Conclusions: In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.

Original languageEnglish (US)
Pages (from-to)264-271
Number of pages8
JournalBJU International
Volume118
Issue number2
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

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Vascular Endothelial Growth Factor Receptor
Sirolimus
Protein-Tyrosine Kinases
Disease-Free Survival
Confidence Intervals
Survival
Therapeutics
Clear-cell metastatic renal cell carcinoma
pazopanib
Karnofsky Performance Status
Proportional Hazards Models
Anemia
Retrospective Studies
Neoplasm Metastasis
Safety

Keywords

  • angiogenesis
  • mTOR inhibitor
  • pazopanib
  • renal cell carcinoma
  • targeted therapy
  • tyrosine-kinase inhibitor

ASJC Scopus subject areas

  • Urology

Cite this

Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors : a single institution experience. / Matrana, Marc R.; Bathala, Tharakeswara; Campbell, Matthew T.; Duran, Cihan; Shetty, Aditya; Teegavarapu, Purnima; Kalra, Sarathi; Xiao, Lianchun; Atkinson, Bradley; Corn, Paul; Jonasch, Eric; Tannir, Nizar M.

In: BJU International, Vol. 118, No. 2, 01.08.2016, p. 264-271.

Research output: Contribution to journalArticle

Matrana, Marc R. ; Bathala, Tharakeswara ; Campbell, Matthew T. ; Duran, Cihan ; Shetty, Aditya ; Teegavarapu, Purnima ; Kalra, Sarathi ; Xiao, Lianchun ; Atkinson, Bradley ; Corn, Paul ; Jonasch, Eric ; Tannir, Nizar M. / Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors : a single institution experience. In: BJU International. 2016 ; Vol. 118, No. 2. pp. 264-271.
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title = "Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors: a single institution experience",
abstract = "Objective: To explore the efficacy and safety of pazopanib in a ‘real-world’ setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited. Patients and Methods: We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables. Results: In all, 88 patients were identified; 74 were evaluable for response: two (3{\%}) had a complete response, 27 (36{\%}) a partial response, 36 (49{\%}) had stable disease and nine (12{\%}) had progressive disease. The median PFS was 13.7 months [95{\%} confidence interval (CI) 8.7–18.3]. PFS was correlated with a Karnofsky Performance Status score of <80 [hazard ratio (HR) 3.26, P < 0.001] and serum lactate dehydrogenase of >1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95{\%} CI 20.2–not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95{\%} CI 3.3–25.7) with VEGFR-TKI and 5 months (95{\%} CI 3.5–15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95{\%} CI 12.9–not reached) and 14.2 months (95{\%} CI 8.1–not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37). Conclusions: In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.",
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T1 - Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors

T2 - a single institution experience

AU - Matrana, Marc R.

AU - Bathala, Tharakeswara

AU - Campbell, Matthew T.

AU - Duran, Cihan

AU - Shetty, Aditya

AU - Teegavarapu, Purnima

AU - Kalra, Sarathi

AU - Xiao, Lianchun

AU - Atkinson, Bradley

AU - Corn, Paul

AU - Jonasch, Eric

AU - Tannir, Nizar M.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - Objective: To explore the efficacy and safety of pazopanib in a ‘real-world’ setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited. Patients and Methods: We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables. Results: In all, 88 patients were identified; 74 were evaluable for response: two (3%) had a complete response, 27 (36%) a partial response, 36 (49%) had stable disease and nine (12%) had progressive disease. The median PFS was 13.7 months [95% confidence interval (CI) 8.7–18.3]. PFS was correlated with a Karnofsky Performance Status score of <80 [hazard ratio (HR) 3.26, P < 0.001] and serum lactate dehydrogenase of >1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95% CI 20.2–not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95% CI 3.3–25.7) with VEGFR-TKI and 5 months (95% CI 3.5–15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95% CI 12.9–not reached) and 14.2 months (95% CI 8.1–not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37). Conclusions: In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.

AB - Objective: To explore the efficacy and safety of pazopanib in a ‘real-world’ setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited. Patients and Methods: We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables. Results: In all, 88 patients were identified; 74 were evaluable for response: two (3%) had a complete response, 27 (36%) a partial response, 36 (49%) had stable disease and nine (12%) had progressive disease. The median PFS was 13.7 months [95% confidence interval (CI) 8.7–18.3]. PFS was correlated with a Karnofsky Performance Status score of <80 [hazard ratio (HR) 3.26, P < 0.001] and serum lactate dehydrogenase of >1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95% CI 20.2–not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95% CI 3.3–25.7) with VEGFR-TKI and 5 months (95% CI 3.5–15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95% CI 12.9–not reached) and 14.2 months (95% CI 8.1–not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37). Conclusions: In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.

KW - angiogenesis

KW - mTOR inhibitor

KW - pazopanib

KW - renal cell carcinoma

KW - targeted therapy

KW - tyrosine-kinase inhibitor

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