LBA8_PR - 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

ABSTRACT Background Pazopanib and sunitinib are oral multi-kinase angiogenesis inhibitors that have shown progression-free survival (PFS) benefit for mRCC patients in clinical trials (NEJM 2007;356:115; JCO 2009;29:475). The COMPARZ study (NCT00720941) was designed to provide a direct comparison of efficacy, safety, and tolerability of pazopanib and sunitinib. Pazopanib N = 557 Sunitinib N = 553 Hazard Ratio 95% CI PFS (IRC, primary) Median (mo) 8.4 9.5 1.0466 0.8982, 1.2195 PFS (investigator) Median (mo) 10.5 10.2 0.998 0.863, 1.154 OS Median (mo) 28.4 29.3 0.91 0.76, 1.08 ORR (IRC) P = 0.03 31% 25% – – Most common AEs (≥40%) Any Grade, % N = 554 N = 548 Risk Ratio 95% CI Diarrhea 63 57 1.09 0.99, 1.20 Fatigue 55 63 0.87 0.79, 0.96 Hypertension 46 41 1.14 1.00, 1.31 Nausea 45 46 0.98 0.86, 1.11 Hand-foot syndrome 29 50 0.59 0.50, 0.68 Other selected class effect AEs Dysgeusia 26 36 0.71 0.60, 0.86 Dyspepsia 14 24 0.58 0.45, 0.75 Hypothyroidism 12 24 0.50 0.38, 0.65 Mucositis 11 26 0.43 0.33, 0.56 ALT increase 31 18 1.74 1.40, 2.17 AST increase 27 18 1.49 1.19, 1.87 Neutropenia 11 27 0.41 0.31, 0.54 Thrombocytopenia 10 34 0.30 0.23, 0.40 Anemia 7 19 0.36 0.26, 0.52 Methods A total of 1110 treatment-naive patients with clear cell mRCC and measurable disease were randomized 1:1 to pazopanib 800 mg QD continuous dosing or sunitinib 50 mg QD in 6-week cycles (4 weeks on followed by 2 weeks off). Primary endpoint was PFS. Based on a planned 631 PFS events by independent review committee (IRC) the study had 80% power to detect non-inferiority of pazopanib to sunitinib where the non-inferiority margin was chosen to exclude a difference of >25% in the hazards. Key secondary endpoints included overall survival (OS), overall response rate (ORR), adverse events (AEs), and quality of life (QoL). Results Patient characteristics were balanced. The upper bound of the 95% CI for PFS by IRC was Conclusions Pazopanib has similar efficacy to sunitinib with a differentiated safety and QoL profile. Disclosure R.J. Motzer: Research Funding : GlaxoSmithKline >10,000 US dollars Research Funding: Pfizer \\ Paid Consultancy: Pfizer T.E. Hutson: Stock ownership: None Membership on an advisory board or board of directors: Pfizer, Bayer, Aveo, Novartis Corporate-sponsored research: Glaxo SK, Pfizer, Aveo, Novartis Other substantive relationships: None M. Staehler: Stock ownership: None Membership on an advisory board or board of directors: advisory board GSK, Pfizer Corporate-sponsored research: GSK, Pfizer Other substantive relationships: None U. Harmenberg: Stock ownership: No Membership on an advisory board or board of directors: /advisory fees from GlaxoSmithKline, Pfizer, Bayer and Novartis. Corporate-sponsored research: No Other substantive relationships: No K. Fife: Stock ownership: none Membership on an advisory board or board of directors: GSK Corporate-sponsored research: GSK, Roche Other substantive relationships: I received financial assistance to attend 2 conferences in 2011 from Bayer and GSK. R. Hawkins: Stock ownership: Wife owns stock in GSK R. Jones: Membership on an advisory board: Past membership with GSK and Pfizer Corporate-sponsored research: GSK and Pfizer. Received funding to participate in commercially sponsored research by both companies, including, but not-limited to, the COMPARZ trial. P. Nathan: Membership on an advisory board or board of directors: GSK Advisory Board J. Merchan: Corporate-sponsored research: GSK, Pfizer, BMS (research –clinical trial- support) P. De Souza: Membership on an advisory board or board of directors: GSK Australia D. Cella: Stock ownership: No, Membership on an advisory board or board of directors: No, Corporate-sponsored research: Yes: Pfizer, Aveo, DSI, GSK, Novartis, Abbott, Other substantive relationships: Consultant: GSK L. McCann: Stock ownership: Yes Membership on an advisory board or board of directors: None Corporate-sponsored research: None Other substantive relationships: GSK employee K. Deen: Stock ownership: Yes Membership on an advisory board or board of directors: None Corporate-sponsored research: None Other substantive relationships: GSK employee T. Choueri: Stock ownership: None Membership on an advisory board or board of directors: Advisory board: Pfizer, GSK, Novartis, Genentech, Aveo, Bayer/Onyx Corporate-sponsored research: Pfizer Other substantive relationships: none–no speaker's bureau. All other authors have declared no conflicts of interest.