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Sunitinib (Sutent) for Renal Cell Cancer. Blocking VEGF in Kidney Cancer is like Blocking Estrogen in Breast Cancer. Blocking VEGF in Kidney Cancer is like Blocking Estrogen in Breast Cancer Anti-VEGF agents have somewhat similar toxicities

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sunitinib sutent for renal cell cancer

Sunitinib (Sutent)for Renal Cell Cancer

Blocking VEGF in Kidney Cancer is like

Blocking Estrogen in Breast Cancer

slide2
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
t e 50 yr old male c kidney cancer
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

sunitinib mechanism of action in rcc
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

slide12

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.

randomization scheme
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)

best response by recist independent central review
Best Response by RECIST (Independent Central Review)

** Sunitinib vs. IFN-: p <0.000001

* 88 patients not yet assessed by central review;

progression free survival independent central review

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

overall survival

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

outcome summary
Outcome Summary

* Sunitinib versus IFN-: p <0.000001

unusual side effects of sunitinib sutent
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
indications for high dose il 2 before january 2006 after january
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
overall survival temsirolimus vs ifn

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.

sorafenib nexavar and sunitinib sutent differences
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
slide33
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