Survival Outcome of Pazopanib and Sunitinib as First-line
T argeted Therapy in Metastatic Renal Cell Carcinoma
A ‘real world’ retrospective review of practice in a tertiary
cancer center in the North-West of England
S. Chow1,3 F. Thistlethwaite1,2 R. Leach1 S. Potter2 M. Pillai1,2 R. Hawkins1,2
1The Christie NHS Foundation Trust, United Kingdom
2The University of Manchester, United Kingdom
3The Clatterbridge Cancer Centre, Wirral, United Kingdom
Abstract
Background: The use of multi-receptor tyrosine kinase inhibitor
(TKI) targeting the tumor angiogenesis pathway
has shifted the treatment paradigm as well as improved
outcomes among patients with mRCC. Sunitinib (S) and
pazopanib (P) are two widely used TKIs options among
treatment naïve patients. Here, we present our experience
and survival outcomes of these two drugs used in a UK
tertiary cancer center.
Methods: mRCC patients who had received either of
these agents as first line therapy were identified through
the Renal Cancer Database (2005-2015). Outcomes of interest
include response rate, progression free survival (PFS)
and overall survival (OS). Subgroup analysis was performed
based on prognostic variables to assess survival impact.
Results: A total of 665 patients were identified (S=397,
P=268). The majority of patients were categorized as having
worse (intermediate to poor) prognostic risk groups
(93% IMDC; 71% MSKCC). Cytoreductive nephrectomy
rate in this population was 62%. Objective response rate
(ORR) was 22%; ORR 25% (S) v 20% (P). Median PFS and
OS of the entire cohort was 10.5 and 16.1 months respectively.
Median OS in good-risk IMDC group reached
47 months but 21 and 7 months in the intermediate and
poor-risk groups respectively. Survival outcomes for both
drug groups were comparable when stratified by prognostic
risks.
Conclusion: In this large population-based retrospective
108 Kidney Cancer Journal
review, the survival performance of either TKI
was impressive and comparable to published evidence
among favorable-risk patients . However, the overall survival
is lower than expected for the entire cohort and is
likely attributable to the high proportion of patients with
less than favorable prognostic risk in this real world cohort
and the correspondingly lower benefits of this subgroups
to these drugs.
Introduction
Renal cell carcinoma is the most common cancer of the
kidney and its incidence is increasing rapidly worldwide.
In England, kidney cancer is the third most common urological
cancer after prostate and bladder cancer with an
incidence in excess of 4000 and 2500 per 100,000 cases
per year for male and female respectively.1 Unfortunately,
around 30% of patients present with advanced or metastatic
disease and relapse rate despite curative surgery is as
high as 40%2,3. The understanding of tumor angiogenesis
pathway in RCC has led to the successful utilization of
anti-angiogenic agents in the last decade. This signalling
process is mediated by binding of stimulatory protein
such as vascular endothelial growth factor (VEGF) and
platelet derived growth factor (PDGF) to the external domain
of transmembrane receptor which in turn activates
the subsequent intracellular tyrosine kinase activity with
cascading effect on cancer cell proliferation and metastasis.
Sunitinib is a first generation small molecule that inhibits
multiple receptor tyrosine kinases. Targets of
sunitinib include vascular endothelial growth factor receptors
(VEGFR1, VEGFR2, and VEGFR3), platelet-derived
growth factor receptors (PDGFR and PDGFR ), and several
other kinase receptors. It received FDA approval for use
in mRCC in 2006. Pazopanib is a second-generation
small-molecule TKI with higher selective activity against
Keywords: renal cell carcinoma, pazopanib, sunitinib, first-line
therapy, survival outcomes.
Corresponding Author: Sien Chow, The Clatterbridge Cancer Centre
NHS Foundation Trust, England, United Kingdom.
Email: shien.chow1@nhs.net
link