1. Genitourinary Oncology ASCO 2009 Toni K. Choueiri, MD Dana-Farber Cancer Institute Harvard Medical School Boston, Massachusetts U.S.A.

2. Bevacizumab plus Interferon-alpha versus Interferon-alpha Monotherapy in Patients with Metastatic Renal Cell Carcinoma: Results of Overall Survival for CALGB 90206 Brian I. Rini 1, Susan Halabi 2,3, Jonathan E. Rosenberg 4, Walter M. Stadler 5, Daniel A.Vaena 6, James N. Atkins 7, Joel Picus 8, Piotr Czaykowski 9, Janice Dutcher 10 and Eric J. Small 4 1. Cleveland Clinic Taussig Cancer Institute, Cleveland, OH 2. Department of Biostatistics / Bioinformatics, Duke University Medical Center, Durham, NC 3. CALGB Statistical Center, Durham, NC 4. University of California San Francisco, San Francisco, CA 5. University of Chicago Medical Center, Chicago, IL 6. University of Iowa, Iowa City, IA 7. Southeast Cancer Control Consortium Inc. 8. Washington University, St. Louis, MO 9. University of Manitoba, Winnipeg, Manitoba; NCI Canada, Kingston, ON, Canada 10. New York Medical College, NY, NY; Eastern Cooperative Oncology Group, Boston, MA

3. Background Bevacizumab (BEV) plus interferon alpha (IFN) demonstrated a superior objective response rate and progression-free survival (PFS) versus IFN monotherapy in metastatic RCC patients in 2 phase III trials 1,2 The primary objective of CALGB 90206 was to compare overall survival (OS) for metastatic RCC patients receiving BEV plus IFN or IFN monotherapy 1. Escudier B et al. Lancet, 2007 2. Rini BI et al. JCO 2008

4. Study Schema RANDOMIZERANDOMIZE IFNA 9 MU TIW IFNA 9 MU TIW + Bevacizumab 10 mg/kg IV q d1 and d15 STRATIFYSTRATIFY Patients stratified for nephrectomy status (yes/no) and MSKCC risk group (0 risk factors vs. 1-2 risk factors vs. 3 or more risk factors)* Eligibility Criteria Confirmed metastatic RCC with a component of clear cell histology Karnofsky PS ≥ 70% Measurable or evaluable disease (by RECIST) No prior systemic treatment Adequate end-organ function No CNS metastases BP < 160/90 with meds No DVT within 1 year or arterial thrombotic event within 6 months Prior nephrectomy not required * Motzer R et al., JCO 20(1), 2002

5. The primary endpoint was OS, defined as the time from randomization to death due to any cause The trial was designed with 86% power to detect a hazard ratio (HR) of 0.76 (assumed median OS improvement 13 to 17 months), assuming a two-sided type I error of 0.05 The primary analysis was an intent-to-treat approach using the stratified log-rank statistic, and the present analysis was based on the target number of 588 deaths Secondary endpoints: Progression-free survival (PFS), objective response rate (RECIST criteria), safety Statistical Methods

6. Patient Disposition Patients consented (n=732) IFNA monotherapy (n=363) Discontinued Treatment (n=346) PD / Death (n=218) Toxicity (n=66) Refused further tx (n=33) Other (n=24) Lost to follow-up (n=4) D/C after achieving CR (n=1) Analyzed (n=363) Bevacizumab + IFNA (n=369) Discontinued Treatment (n=349) PD / Death (n=200) Toxicity (n=80) Refused further tx (n=40) Other (n=25) Lost to follow-up (n=2) D/C after achieving CR (n=2) Analyzed (n=369) Never started tx (n=13) Never started tx (n=3)

7. Baseline Demographics and Clinical Characteristics (n=732) Bevacizumab plus IFN (n=369) IFN monotherapy (n=363) Sex – no. (%) Male Female 269 (73%) 100 (27%) 239 (66%) 124 (34%) Median Age, years (inter-quartile range) 61 (56-70) 62 (55-70) ECOG performance status – no. (%) 0 1 2 230 (62%) 132 (36%) 7 (2%) 227 (62%) 133 (37%) 3 (1%) Previous nephrectomy – no. (%)312 (85%) 308 (85%) Previous radiation therapy – no. (%)35 (9%) 38 (10%) Common Sites of Metastases Lung Lymph node Bone Liver 252 (68%) 130 (35%) 104 (28%) 74 (20%) 254 (70%) 129 (36%) 109 (30%) 73 (20%) Number of adverse risk factors 0 (favorable) 1-2 (intermediate) ≥ 3 (poor) 97 (26%) 234 (64%) 38 (10%) 95 (26%) 231 (64%) 37 (10%)

8. ---- BEV/IFN: Median OS 18.3 months IFN: Median OS 17.4 months Kaplan-Meier Overall Survival by Treatment Arm

9. Overall Survival by MSKCC Risk Status * Median OS (months) Risk Group % BEV/IFN IFN HR Favorable (0 risk factors)2632.5 33.5 0.89 (p = 0.524) Intermediate (1-2 risk factors)6417.7 16.1 0.87 (p = 0.174) Poor (≥ 3 risk factors)106.6 5.7 0.76 (p = 0.25) * Motzer R et al., JCO 20(1), 2002

10. Second-line Therapy Received in Patients who Discontinued Protocol Therapy for Any Reason Other Than Death Bevacizumab + IFN (n=351) IFN monotherapy (n=350) Percentage of patients receiving any second-line therapy 54% 62% VEGF-targeted therapy37% 46% Bevacizumab 6% 14% Chemotherapy18% 14% Investigational therapy11% 18% Cytokines13% 14% * Fifty-six percent of patients overall received at least one subsequent systemic therapy

11. Median OS (months) according to treatment arm and subsequent therapy Bevacizumab + Interferon InterferonTotal (unstratified log-rank p comparing arms) Stratified HR Received 2 nd -line therapy (n=408) 31.426.828.2 (p=0.079) 0.80 (p=0.055) Did not receive 2 nd - line therapy (n=324) 13.19.110.2 (p=0.059) 0.82 (p=0.108) Total18.317.418.1 (p=0.097) 0.86 (p=0.069)

12. Variable Received non protocol treatment* (n=408) Did not receive non protocol treatment (n=324 ) p-value Gender Male Female 70% 30% 79% 31%0.687 Median Age, years (inter-quartile range) 61 (55-69) 62 (56-71)0.019 ECOG PS 0 1 2 67% 32% 1% 56% 42% 2% 0.012 Previous nephrectomy 88% 80%0.004 Previous XRT 12% 8%0.064 Sites of Metastases Lung Lymph node Bone Liver 70% 35% 29% 17% 68% 36% 29% 24% 0.572 0.756 0.935 0.020 MSKCC risk group 0 (favorable) 1-2 (intermediate) ≥ 3 (poor) 29% 64% 6% 22% 62% 15% <.001 Baseline characteristics of patients according to subsequent therapy * There was no difference in baseline characteristics for patient who received subsequent therapy by treatment assignment

13. Forest Plot of Overall Survival in Select Subgroups BEV/IFN betterIFN better

14. Kaplan-Meier Progression-Free Survival by Treatment Arm -- Median PFS 8.4 months Median PFS 4.9 months HR= 0.71 (95% CI=0.6-0.8)

15. Objective Response Note: patients with measurable disease only Bev + IFN (n=325)IFN (n=314) Overall Response rate25.5% [95% CI = 20.9-30.6] 13.1% [95% CI = 9.5-17.3] CR 3.7% 1.9% PR23.4%12.7% p < 0.0001 Duration of response11.9 months [95% CI = 8.3 – 14.8] 9.7 months [95% CI = 7.6 – 19.8] p = 0.362

16. Adverse event Bevacizumab + IFN (n=366) IFN (n=352) Any grade 3/4 adverse event79% 61% Fatigue/asthenia/malaise37% 30% Anorexia17% 8% Proteinuria 15%<1% Hypertension 11% 0% Hemorrhage 2%<1% Venous thromboembolism 2% 1% Gastrointestinal perforation <1% 0% Arterial ischemia 1% 0% Frequency of selected grade 3 or 4 AEs

17. Conclusions Overall survival is greater in patients with metastatic clear cell RCC receiving bevacizumab plus interferon as initial systemic therapy compared to interferon alone, but does not meet pre- defined criteria for significance Although the effect of bevacizumab plus IFN on OS is preserved regardless of subsequent treatment, the most robust OS is achieved in patients with favorable underlying disease biology who are able to receive subsequent therapy The combination of bevacizumab and IFN as initial therapy in metastatic RCC patients results in a significantly greater progression-free survival and objective response rate versus IFNA monotherapy Toxicity is greater in the combination therapy arm, including more fatigue, anorexia, hypertension and proteinuria

18. Final results of the phase III, randomised, double-blind AVOREN trial of first-line bevacizumab + interferon-  2a in metastatic renal cell carcinoma Escudier B, Bellmunt J, Negrier S, Bajetta E, Melichar B, Bracarda S, Ravaud A, Golding S, Jethwa S on behalf of the AVOREN investigators

19. *PFS is the primary endpoint for regulatory approval in the USA Escudier, et al. Lancet 2007 AVOREN study design Endpoints –primary:* OS –secondary: PFS, TTP, TTF, RR, safety Treatment –bevacizumab/placebo 10mg/kg i.v. q2w –IFN 9MIU s.c. t.i.w. (maximum 52 weeks) IFN  + Bevacizumab (n=327) IFN  + placebo (n=322) PD Nephrectomised patients with advanced RCC (n=649) Stratification: Country MSKCC risk group 1:1 PD

20. Summary of published AVOREN data Final analysis of PFS performed at the time of the interim analysis –significant increase from 5.4 to 10.2 months when bevacizumab is combined with IFN (HR=0.63; p=0.0001) 1 –good safety profile By reducing the IFN dose for safety issues –PFS benefit is maintained 2 –decreased incidence of grade 3/4 events 2 1. Escudier, et al. Lancet 2007; 2. Melichar, et al. Ann Oncol 2008

21. Independent review of PFS and ORR Investigator 1 IRC 2 IFN + Bevacizumab (n=327) IFN + placebo (n=322) IFN + Bevacizumab (n=288) IFN + placebo (n=281) ORR (%)31133112 p value<0.0001 Median PFS (months)10.25.410.45.5 HR (95% CI)0.63 (0.52–0.75)0.57 (0.45–0.72) p value<0.0001 1. Escudier, et al. Lancet 2007; 2. Roche, data on file

22. Objectives Final analysis of OS Clinical cut-off September 2008 Median follow-up: 22 months Statistical considerations –required 445 events from 649 randomised patients –80% power to detect an improvement in OS from 13 to 17 months –corresponding to an HR of 0.76 at a two-sided overall significance level of 0.05

23. Final OS: unstratified and stratified analyses Cox regressionp value HR95% CILog-rankWilcoxon Unstratified0.910.76–1.100.33600.2046 Stratified*0.860.72–1.040.12910.0969 *Stratified by Motzer score and region

24. Probability of survival Final OS Patients at risk (n) IFN + Bevacizumab 3272782371941571248427 IFN + placebo 3222622161771411137822 21.323.3 06121824303642 Time (months) 1.0 0.8 0.6 0.4 0.2 0 IFN + Bevacizumab (n=327) IFN + placebo (n=322) HR=0.86 (95% CI: 0.72–1.04) p=0.1291 (stratified*) *Stratified by Motzer score and region

25. Multiple Cox regression analysis for OS A multiple Cox regression model controls for several predetermined baseline prognostic factors that influence survival independent of treatment Variables included in the analysis –gender, age, Motzer score, location of metastases (lung, bone, liver), body weight loss, number of sites, baseline SLD, region, baseline VEGF, and some lab values (albumin, creatinine, alkaline phosphatase, WBC count, platelets) Adjustment for these factors resulted in an improved treatment effect –HR=0.78 (95% CI: 0.63–0.96); p=0.0219

26. Final OS in reduced-dose IFN population 26.023.3 Probability of survival 1.0 0.8 0.6 0.4 0.2 0 06121824303642 Time (months) Patients at risk (n) Bevacizumab + reduced-dose IFN131116102 85 72 573816 Bevacizumab + IFN3272782371941571248427 Bevacizumab + reduced-dose IFN (n=131) Bevacizumab + IFN (n=327)

27. Censoring patients at time of crossover (n=13) IFN + Bevacizumab (n=327) IFN + placebo (n=322) Patients with event, n (%)220 (67.3)224 (69.6) Patients without events, n (%)107 (32.7)98 (30.4) Median OS, months (95% CI)23.3 (20–27)20.8 (18–24) HR (95% CI)0.84 (0.70–1.02) p value (Log-rank test)*0.0766 *Stratified by Motzer score and region

28. Censoring crossover patients Probability of survival Patients at risk (n) Bevacizumab + IFN3272782371941571248427 IFN + placebo 3222622161731311016919 06121824303642 Time (months) 1.0 0.8 0.6 0.4 0.2 0 23.320.8 IFN + Bevacizumab (n=327) IFN + placebo (n=322) HR=0.84 (95% CI: 0.70–1.02) p=0.0766* *Stratified by Motzer score and region

29. Summary of subsequent medical therapies Treatment, n (%) IFN + Bevacizumab (n=327) IFN + placebo (n=322) Total patients with ≥1 treatment180 (55) 202 (63) VEGF inhibitors Sunitinib83 (25)92 (29) Sorafenib60 (18)50 (16) Bevacizumab10 (3)12 (4) Other* 7 (2) 6 (2) mTOR inhibitors ‡ 14 (4) 6 (2) Cytokines32 (10)52 (16) Chemotherapy § 28 (9)47 (15) *Protein TKI, pazopanib, erlotinib, blinded sorafenib, blinded sunitinib, angiogenesis inhibitors NOS, VEGF inhibitor NOS ‡ Temsirolimus, everolimus (RAD001) § Antimetabolites, vinca alkaloids and antineoplastic agents

30. Regional variation in subsequent treatment with TKIs IFN + BevacizumabIFN + placebo Therapy Western Europe (n=180) Eastern Europe and other (n=147) Western Europe (n=177) Eastern Europe and other (n=145) TKIs, n (%) Sunitinib52 (29)31 (21)64 (36)28 (19) Sorafenib51 (28)9 (6)48 (27)2 (1)

31. Regional variation in OS IFN + BevacizumabIFN + placebo Western Europe (n=180) Eastern Europe and other (n=147) Western Europe (n=177) Eastern Europe and other (n=145) Events, n (%)120 (67)100 (68)125 (71)99 (68) Median OS, months (95% CI)24.5 (21–29)23.1 (17–27)23.7 (21–28)17.1 (13–22) HR (95% CI)*0.93 (0.71–1.21)0.92 (0.71–1.20) p value (log-rank)* 0.59220.5336 *Stratified by Motzer score and region

32. OS by post-protocol therapies IFN + Bevacizumab vs IFN + placebo (n) Median OS IFN + Bevacizumab (months) IFN + placebo (months) HR (95% CI) Subsequent TKI* ‡ 113 vs 12038.633.60.80 (0.56–1.13) Subsequent sunitinib83 vs 9243.639.70.88 (0.58–1.35) Subsequent sorafenib60 vs 5038.630.70.73 (0.44–1.20) *Subsequent therapy defined as any post-protocol therapy, any line (before or after PD) ‡ TKIs include sunitinib, sorafenib, pazopanib, erlotinib, blinded sorafenib, blinded sunitinib and unspecified protein TKI

33. Subgroup analysis of OS in AVOREN 0.20.5125 Baseline risk factorTotal (n)HR 95% CI All patients6490.860.72–1.04 410 239 0.78 0.99 Age (years) <65 ≥65 0.61–0.99 0.73–1.35 Baseline VEGF > median No Yes 192 0.74 0.88 0.50–1.10 0.62–1.24 192 457 0.90 0.84 Sex Female Male 0.64–1.27 0.66–1.05 Motzer score Favourable Intermediate Poor 180 366 55 0.86 0.83 0.86 0.57–1.30 0.65–1.06 0.47–1.59 Per cent body weight loss  10 >10 501 81 0.88 0.60 0.70–1.09 0.35–1.04

34. No. of metastatic sites 1 2 >2 152 242 252 0.81 1.02 0.74 0.52–1.27 0.73–1.41 0.55–0.99 Subgroup analysis of OS in AVOREN (cont’d) Baseline risk factorTotal (n)HR 95% CI 0.70–1.09 0.58–1.32 Bone metastases No Yes 521 125 0.87 0.88 565 81 0.88 0.68 Tumour in lung only No Yes 0.72–1.08 0.36–1.28 0.20.5125 Lung metastases No Yes 173 473 1.10 0.77 0.73–1.66 0.61–0.96 Liver metastases No Yes 508 138 0.76 1.30 0.62–0.95 0.85–1.98

35. Probability of survival Time (months) 1.0 0.8 0.6 0.4 0.2 0 06121824303642 Patients at risk (n) Bevacizumab + IFN2582282041691401127724 IFN + placebo 250211173140111 916117 Median OS IFN + Bevacizumab (n=258) IFN + placebo (n=250) HR=0.76 (95% CI: 0.62–0.95) p=0.0155* OS in patients without liver metastases at baseline 21.427.5 *Stratified by Motzer score and region

36. Conclusions Although not statistically significant, a trend towards improved OS was observed with bevacizumab + IFN combination. The results have been confounded by –post-protocol bevacizumab –subsequent therapies Patients with bevacizumab + reduced doses of IFN had similar OS to the whole bevacizumab + IFN population Treatment effect is significant when adjusted for prognostic factors This analysis confirms the activity of this treatment in first line metastatic RCC with good or intermediate risk

37. Phase III Trial of Pazopanib in Locally Advanced and/or Metastatic Renal Cell Carcinoma Cora N. Sternberg, 1 Cezary Szczylik, 2 Eun S. Lee, 3 Pamela Salman, 4 Jozef Mardiak, 5 Ian D. Davis, 6 Lini Pandite, 7 Mei Chen, 8 Lauren McCann, 8 Robert E. Hawkins 9 1 San Camillo and Forlanini Hospitals, Rome, Italy; 2 Military Institute of Medicine, Warsaw, Poland; 3 National Cancer Center, Gyeonggi-do, Korea; 4 Fundación Arturo López Pérez, Santiago, Chile; 5 National Oncological Institute, Klenová, Bratislava, Slovakia; 6 Austin Hospital, Melbourne, Australia; 7 GlaxoSmithKline, Inc., Research Triangle Park, NC, USA; 8 GlaxoSmithKline, Inc., Collegeville, PA, USA; 9 University of Manchester and Christie Hospital NHS Foundation Trust, Manchester, UK

38. Pazopanib Kinase affinity profile K i app (nM) VEGFR-115 VEGFR-28 VEGFR-310 PDGFR-α30 PDGFR-β14 c-Kit2.4 An oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-Kit Clinical efficacy demonstrated in advanced RCC in a Phase II study 1 1. Hutson TE, et al. J Clin Oncol. 2007;25(suppl):18S:5031.

39. A Global, Randomized, Double-Blind Study to Evaluate Efficacy and Safety of Pazopanib in Advanced RCC (VEG105192) 80 Sites in 22 countries Enrolled: Apr 06 - Apr 07 Europe Austria Czech Republic Estonia Ireland Italy Latvia Lithuania Poland Russia Slovakia Tunisia England Ukraine South America Argentina Brazil Chile Asia/Pacific Australia China/HK India Korea New Zealand Pakistan

40. Patient Eligibility Locally advanced and/or metastatic RCC Clear-cell histology Treatment-naive or failure of 1 prior cytokine therapy Measurable disease by RECIST ECOG PS 0 or 1 Adequate organ function Age  18 years

41. Study Design Pazopanib 800 mg qd (n = 290) Matching Placebo (n = 145) Option to receive pazopanib via an open-label study at progression Stratification ECOG PS 0 vs 1 Prior nephrectomy Rx-naive (n = 233) vs 1 cytokine failure (n = 202) Patients with advanced RCC (N = 435) Randomization 2:1

42. Endpoints and Analysis Plan Primary: –Progression-free survival (PFS) > 90% power to detect 80% improvement in median PFS Adequately powered in the treatment-naive, cytokine-pretreated subpopulations Secondary: –Overall survival (OS) 90% power to detect a 50% improvement in median OS –Overall response rate (ORR), duration of response, safety, health-related quality of life (HRQoL) Analysis Plan: –One single analysis for PFS, one planned interim analysis for OS (at the time of PFS analysis) Clinical cutoff: May 23, 2008 PFS and ORR results presented here are based on independent review.

43. Pazopanib (n = 290) Placebo (n = 145) Median age (range), yrs59.0 (28 – 85)60.0 (25 – 81) Gender, % male6875 Metastatic sites,% Lung Lymph node Bone Liver 74 54 28 26 73 59 26 22 Number of organs involved, % 1 & 2 ≥ 3 45 55 48 52 ECOG PS 0 / 1, %42 / 5841 / 59 MSKCC risk category, % Favorable Intermediate Poor / Unknown 39 55 3 / 3 39 53 3 / 4 Demographic and Baseline Disease Characteristics

44. PFS in Overall Study Population 1.0 0.0 0.2 0.4 0.6 0.8 0 5 10 15 20 Months Proportion Progression-Free Patients at risk Pazopanib 29015976296 Placebo 14538142 Hazard Ratio = 0.46 95% CI (0.34, 0.62) P value < 0.0000001 Median PFS Pazopanib:9.2 mo Placebo:4.2 mo Pazopanib Placebo

45. PFS in Treatment-Naive Subpopulation 1.0 0.0 0.2 0.4 0.6 0.8 0 5 10 15 20 Months Proportion Progression-Free Patients at risk Pazopanib 1553439111 Placebo 782272 Hazard Ratio = 0.40 95% CI (0.27, 0.60) P value < 0.0000001 Median PFS Pazopanib:11.1 mo Placebo: 2.8 mo Pazopanib Placebo

46. PFS in Cytokine-Pretreated Subpopulation 1.0 0.0 0.2 0.4 0.6 0.8 0 5 10 15 20 Months Proportion Progression-Free Patients at risk Pazopanib 1357537185 Placebo 67167 Hazard Ratio = 0.54 95% CI (0.35, 0.84) P value < 0.001 Median PFS Pazopanib: 7.4 mo Placebo: 4.2 mo Pazopanib Placebo

47. Subgroup Analysis of PFS Primary analysis MSKCC risk: Favorable MSKCC risk: Intermediate Female Male Age < 65 yrs Age  65 yrs ECOG PS 0 ECOG PS 1 0.20.40.60.81.0 Favors pazopanibFavors placebo 1.2 Hazard Ratio (95% CI) Baseline Factor P < 0.001 by log-rank test for all.

48. Tumor Response Pazopanib (n = 290) Placebo (n = 145) ORR (CR + PR), % Overall population Treatment-naive Cytokine-pretreated 30 32 29 343343 Duration of response, weeks59 ─

49. Interim Analysis of Overall Survival O’Brien-Fleming boundary for futility / superiority: P = 0.201 / 0.004 (1-sided) 1.0 0.0 0.2 0.4 0.6 0.8 05101520 Months Proportion Surviving Patients at risk Pazopanib 29025421411520 1 Placebo 14511593526 Hazard Ratio = 0.73 95% CI (0.47, 1.12) P value = 0.02 (1-sided) Median OS Pazopanib: 21.1 mo Placebo: 18.7 mo Pazopanib Placebo 25 48% of placebo patients received pazopanib after PD

50. Most Common Adverse Events (  10%) Median exposure: pazopanib 7.4 (0 - 23) vs placebo 3.8 (0 - 22) months Adverse Event Pazopanib (n = 290) %Placebo (n = 145) % All GrsGr 3Gr 4All GrsGr 3Gr 4 Any event a 9233774146 Diarrhea523< 19 0 Hypertension404010< 10 Hair color changes38< 10300 Nausea26< 10900 Anorexia222010< 10 Vomiting212< 1820 Fatigue1920811 Asthenia1430800 Hemorrhage b 131< 1500 Abdominal pain1120100 Headache1000500 a 4% of patients in pazopanib arm and 3% of patients in placebo arm had grade 5 adverse events. b Included hemorrhage from all sites; 1% patients in pazopanib arm had grade 5 events.

51. Selected Class Effects a Pazopanib (n = 290) Placebo (n = 145) Adverse EventAll Grades, % Proteinuria90 Hypothyroidism70 Hand-foot syndrome6(< 1) Mucositis / Stomatitis4 / 4< 1 / 0 Arterial thromboembolic3b3b 0 a Associated with multi-target receptor tyrosine kinase inhibitors. b 2% of arterial thromboembolic events were  grade 3.

52. Health-Related Quality of Life Global health status / quality of life was compared using 3 prespecified HRQoL indices –EORTC-QLQ-C30 –EQ-5D Index –EQ-5D-VAS There was no difference between treatment with pazopanib and placebo (P > 0.05) at any of the on-therapy assessment time points

53. Pazopanib Summary Significant improvement in PFS and RR compared with placebo in treatment-naive and cytokine-pretreated patients Significant improvement in PFS was observed in all subgroups The safety profile was acceptable Results indicate a favorable risk / benefit profile in the treatment of patients with treatment-naive and cytokine- pretreated advanced RCC Interim OS data are not yet mature