Sunitinib (Sutent) for Renal Cell Cancer - PowerPoint PPT Presentation

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Sunitinib (Sutent) for Renal Cell Cancer

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Sunitinib (Sutent) for Renal Cell Cancer
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Sunitinib (Sutent) for Renal Cell Cancer

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  1. Sunitinib (Sutent)for Renal Cell Cancer Blocking VEGF in Kidney Cancer is like Blocking Estrogen in Breast Cancer

  2. Blocking VEGF in Kidney Cancer is like Blocking Estrogen in Breast Cancer • Anti-VEGF agents have somewhat similar toxicities • High-Dose Interleukin-2 can cure some patients with metastatic kidney cancer

  3. T.E., 50 yr old male c kidney cancer • July 2004 Nephrectomy clear cell cancer venous margin + • December 2004 Partial excision tumor in vena cava • February 2005 Brain metastases Rx cyberknife • April 2005 Liver, lung metastases Rx Subcu IL-2---PD • August 2005 Rx sorafenib --PD • October 2005 GI bleeding bowel invasion Rx weekly transfusion • December 2005 Rx sunitinib 50mg/day • April 2006 Grade 2-3 Hand-foot syndrome dose 37mg/day • June 2006 CT’s show 47% recist PR in lung mets leaves town for 3000 mile motocycle trip

  4. Sunitinib Mechanism of Action in RCC Loss of VHL protein function ↑VEGF ↑PDGF VEGF PDGF VEGFR PDGFR Pericyte/fibroblast/ vascular smooth muscle Vascular endothelial cell Sunitinib Vascular permeability Cell survival, proliferation, migration Vascular formation, maturation RCC pathogenesis and progression

  5. Phase 3 Randomized Trial of Sunitinib malate (SU11248) versus Interferon-alfa as First-line Systemic Therapy for Patients with Metastatic Renal Cell Carcinoma RJ Motzer, TE Hutson, P Tomczak, MD Michaelson, RM Bukowski, O Rixe, S Oudard, ST Kim, CM Baum, RA Figlin and the SU11248 Study Group Supported by Pfizer Inc.

  6. Randomization Scheme R A N D O M I Z A T I O N • N=750 • Stratification Factors: • LDH >1.5 vs. 1.5 x ULN • ECOG PS 0 vs. 1 • Presence vs. absence of nephrectomy Sunitinib (n=375) IFN- (n=375)

  7. Patient Characteristics

  8. Best Response by RECIST (Independent Central Review) ** Sunitinib vs. IFN-: p <0.000001 * 88 patients not yet assessed by central review;

  9. 1.0 Sunitinib (n=375) Median: 11 months 0.9 (95% CI: 10, 12) IFN- (n=375) 0.8 Median: 5 months (95% CI: 4, 6) 0.7 0.6 Progression Free Survival Probability 0.5 0.4 0.3 0.2 Hazard Ratio = 0.415 (95% CI: 0.320, 0.539) 0.1 p < 0.00001 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Time (Months) Progression-free Survival(Independent Central Review) No. at Risk Sunitinib: 235 90 32 2 No. at Risk IFN-: 152 42 18 0

  10. Sunitinib (n=375) Median not reached 1.0 IFN- (n=375) Median not reached 0.9 0.8 0.7 0.6 Overall Survival Probability 0.5 0.4 0.3 0.2 Hazard Ratio = 0.65 95% CI (0.449, 0.942) 0.1 p = 0.0219* 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Time (Months) Overall Survival * The nominal level of significance for this pre-planned analysis was p <0.0031 No. at Risk Sunitinib: 341 190 84 15 1 No. at Risk IFN-: 296 162 66 10 0

  11. Laboratory Abnormalities

  12. Treatment-Related Adverse Events

  13. Sunitinib Dermatological Toxicity

  14. Outcome Summary * Sunitinib versus IFN-: p <0.000001

  15. Unusual Side effects of Sunitinib (sutent) • Hand-foot syndrome with skin blisters or ulcers • Hypothyroidism and adrenal insufficiency • Decreased cardiac function?? • Hypertension • Pulmonary hemorrhage seen in lung cancer patients • Hypophosphatemia

  16. High-dose IL-2 at California Pacific: 5 of 50 patients in 10 years

  17. Renal cell cancer Age < 65 P.S 0--1.5 Brain metastases if resected Motivated patient Clear cell renal cell Age <55 P.S. 0--0.5 No brain metastses Very motivated patient Clinical trials if available Indications for high-dose IL-2before January 2006 after January

  18. TEMSR ± IFN 3-Arm Phase III Study Overall Survival Temsirolimus vs IFN 1.00 0.75 Arm 2: Temsirolimus Probability of survival 0.50 Arm 1: IFN 0.25 Arm 3: IFN + temsirolimus 0 0 5 10 15 20 25 30 35 Time from randomization (months) Adapted from:Hudes G et al. Presented at: ASCO; June 2-6, 2006; Atlanta, GA.

  19. Sorafenib given BID Sorafenib probably less toxic Dispensed via mail-order pharmacies only Onyx/Bayer pharmaceuticals In trial in combinations Sunitinib given daily 4 weeks on, 2 weeks off Sunitinib probably more potent but more toxic with fatigue and mild hematologic toxicity Dispensed via local pharmacies Sugen/Pfizer pharmaceuticals In trial in combinations Sorafenib (Nexavar) and Sunitinib (Sutent):Differences

  20. Blocking VEGF in Kidney Cancer is like Blocking Estrogen in Breast Cancer • Anti-VEGF agents have somewhat similar toxicities • High-Dose Interleukin-2 can cure some patients with metastatic kidney cancer