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Head-to-head study of GSK’s Votrient®(pazopanib) vs sunitinib in advanced renal cell carcinoma meets primary endpoint; findings presented at ESMO 2012 Congress

GSK
Posted on: 01 Oct 12

Head-to-head study of GSK’s Votrient® (pazopanib) vs sunitinib in advanced renal cell carcinoma meets primary endpoint; findings presented at ESMO 2012 Congress

GlaxoSmithKline (GSK) plc announced today that the pivotal Phase III study COMPARZ (COMParing the efficacy, sAfety and toleRability of paZopanib vs. sunitinib) has met its primary endpoint. In the open-label, head-to-head study, pazopanib demonstrated non-inferiority to sunitinib in terms of progression free survival. Patients in the study were treated for advanced renal cell carcinoma (aRCC) with a component of clear cell histology and had received no prior systemic therapy for advanced or metastatic renal cell carcinoma. The findings were presented by lead investigator, Robert J. Motzer, MD, of the Memorial Sloan-Kettering Cancer Center during the 1 October Presidential Symposium of the ESMO 2012 Congress of the European Society for Medical Oncology held in Vienna, Austria.1 In the study, 1110 patients were randomised to receive treatment with either pazopanib or sunitinib at their respective, approved treatment doses (pazopanib – 800mg/daily; sunitinib - 50 mg/daily for 4 weeks followed by 2 weeks off treatment). Treatment was continued in both arms until patients showed signs of disease progression, unacceptable toxicity, voluntarily withdrew from study or died due to any cause. The primary endpoint was non-inferiority in progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), duration of response, health-related quality of life (QoL), safety and medical resource utilisation.1

According to results based on independent review, COMPARZ showed that pazopanib was non-inferior to sunitinib with a hazard ratio for PFS of 1.047 (95% CI 0.898, 1.220); predefined criterion for non-inferiority was the upper bound of a two-sided 95% CI of 1.25. Median PFS was 8.4 months (95% CI 8.3, 10.9) for pazopanib compared to sunitinib at 9.5 months (95% CI 8.3, 11.1). The secondary endpoint of ORR (by independent review) showed an ORR of 31 percent in the pazopanib arm compared to 25 percent in the sunitinib arm, (p = 0.032). Interim analysis of OS data showed that the pazopanib vs sunitinib hazard ratio for OS was 0.908 (95% CI 0.762, 1.082; p-value = 0.275) [median OS of 28.4 months (95% CI 26.2, 35.6) compared to sunitinib at 29.3 months (95% CI 25.3, 32.5)].1 Study findings also showed there was a statistically significant outcome in favour of pazopanib for eleven of the fourteen domains from four Quality of Life (QOL) instruments which included measures of fatigue, mouth and throat soreness, as well as hand and foot soreness among other measures.1

The most common adverse events (= 30%, all grades) in this study for pazopanib compared to sunitinib, respectively, included: diarrhoea (63% vs. 57%); fatigue (55% vs. 63%); hypertension (46% vs. 41%); nausea (45% vs. 46%); decreased appetite (37% vs. 37%); ALT increase (31% vs. 18%); hair colour changes (30% vs. 10%); hand-foot syndrome (29% vs. 50%); taste alteration (26% vs. 36%); and, thrombocytopenia (10% vs. 34%).1

Forty two percent of patients in the pazopanib arm and 41% in the sunitinib arm had serious adverse events. Serious adverse events (AE) occurring in 3% or more of patients in the pazopanib arm were ALT increase and AST increase. Serious AEs occurring in 3% or more of patients in the sunitinib arm were pyrexia and thrombocytopenia.

Thirteen subjects (2%) had fatal AEs in the pazopanib arm and 19 subjects (3%) in the sunitinib arm had fatal AEs. There was no predominant fatal event. Eleven subjects had fatal AEs that were considered drug-related by Investigator assessment: 3 (<1%) in the pazopanib arm and 8 (1%) in the sunitinib arm.“We are pleased with the results of the COMPARZ study and look forward to sharing our findings with the physicians who treat advanced renal cell carcinoma,” said Paolo Paoletti, MD, President of GSK Oncology. “There has been limited information on the direct comparison of therapeutic agents such as pazopanib and sunitinib and we undertook the study in hopes of providing insights that will support the treatment decisions physicians make.”

About VOTRIENT® (pazopanib)
Votrient® (pazopanib) was first approved by the US Food and Drug Administration for the treatment of patients with advanced renal cell carcinoma (aRCC) in October 2009 and received conditional marketing authorisation in the EU in June 2010. Pazopanib is now approved in more than 75 countries. Severe and fatal hepatotoxicity has been observed in clinical trials with pazopanib.2 Hepatic function should be monitored and dosing interrupted, reduced, or discontinued as recommended.2 Potentially serious adverse reactions with pazopanib included hepatoxicity, QT prolongations and torsades de pointes, cardiac dysfunction, hemorrhagic events, arterial and venous thrombotic events, gastrointestinal perforation and fistula, reversible posterior leukoencephalopathy syndrome, hypertension, wound healing, hypothyroidism, proteinuria, infection, increased toxicity with other cancer therapies, and fetal harm.2

The most common adverse events associated with pazopanib (all grades, incidence >20%) seen in patients treated for aRCC are: diarrhoea, hair colour change, hypertension, nausea, fatigue and anorexia.2 Please refer to the Summary of Product Characteristics for further information.

For more information about pazopanib, including approved uses, please visit http://www.gsk.com/products/prescription-medicines/votrient.htm

About GlaxoSmithKline
GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better, and live longer. For company information, visit GlaxoSmithKline at http://www.gsk.com

GlaxoSmithKline Enquiries:
UK Media Enquiries:
Philippa Manning
+44 (0) 7909 002344
(London)
Vanessa Say (Packer Forbes)
020 7036 8550
(London)
References
1. Motzer RJ, Hutson TE, Reeves J, et al. Randomized, open label, phase III trial of pazopanib versus sunitinib in first-line treatment of patients with metastatic renal cell carcinoma (mRCC); Results of the COMPARZ trial. Abstract and oral presentation at European Society of Medical Oncology Congress 2013. Abstract no. LBA8_PR
2. Pazopanib Summary of Product Characteristics. September 2012

For more information:
http://www.gsk.com

Editor's Details

Vanessa Say
Packer Forbes

Last updated on: 01/10/2012

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