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BJU Int. 2016 Aug;118(2):264-71. doi: 10.1111/bju.13374. Epub 2015 Dec 13.

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.

Author information

1
Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
2
Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
3
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
4
Hematology and Oncology Fellowship, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
5
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
6
Division of Emergency Medicine, Baylor College of Medicine, Houston, TX, USA.
7
Division of Quantitative Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
8
Clinical Pharmacy Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

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.

KEYWORDS:

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

PMID:
26573089
PMCID:
PMC4870151
DOI:
10.1111/bju.13374
[Indexed for MEDLINE]
Free PMC Article

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