Advanced Hepatocellular and Renal Cell Carcinomas: Updated Data in Specific Patient Populations

Advanced Hepatocellular andRenal Cell Carcinomas: Updated Data in

Specific Patient Populations

Based on presentations from the44th Annual Meeting of the

American Society of Clinical Oncology (ASCO)May 30-June 3, 2008

Chicago, Illinois

Responses to Sorafenib According to Resistance

IM-RES(n=6)

IM/SU-RES(n=23)

Overall (n=29)

CR 0 (0%) 0 (0%) 0 (0%)

PR 1 (17%) 3 (13%) 4 (14%)

SD 3 (50%) 15 (65%) 18 (62%)

Disease control:CR+PR+SD 4 (67%) 18 (78%) 22 (76%)

Adapted from Wiebe et al. ASCO 2008, abstract 10502.

Toxicities Developed After Sorafenib Treatment (n=29)

Grade 3(% patients)

Grade 4(% patients)

Hypertension 24 -

Hand-foot 24 -

Rash 17 -

Diarrhea 10 -

Fatigue 7 -

Hemorrhage 7 -

Thrombosis - 3

Perforation 3 -

Anemia 3 -

Adapted from Wiebe et al. ASCO 2008, abstract 10502.

Cardiac-related Grade ≥3 Adverse Events

Adverse events (%) ≥65 years(n=1131)

<65 years(n=1361)

Hypertension 5 5

Cardiac ischemia 1 1

Hypotension 1 0.3

Cardiac arrhythmia 1 0.2

Adapted from Bukowski et al. ASCO 2008, abstract 5045.

Cost-effectiveness Results

First-line treatment Best supportive care

Sorafenib

Life-years gained(discounted)

Mean* 1.06 1.59Standard deviation 0.10 0.18

Total costs(discounted)

Mean* $8,161 $41,782Standard deviation $1,408 $3,292

Incermental LYG 0.53

Incermental costs $33,621

Incermental cost per LYG $63,436

*Probabilistic mean

Adapted from Muzbek et al. ASCO 2008, abstract 6527.

RECIST Response by ECOG PS

Percentage of patients

PS 0 PS 1-2

sorafenib (n=161)

Placebo (n=164)

Sorafenib (n=138)

Placebo (n=139)

ORR (CR + PR) 2.5 0.6 2.2 0.7

SD 77.6 70.1 62.3 64.0

PD 13.7 25.6 23.2 22.3

Not assessable 6.2 3.7 12.3 13.0

DCR 46.6 36.0 39.9 26.6

Adapted from Raoul et al. ASCO 2008, abstract 4587.

SHARP: Baseline Patient Characteristics

MVI/EHS present(n=421)

MVI/EHS absent(n=181)

CharacteristicsSorafenib (n=209)

Placebo (n=90)

Sorafenib (n=90)

Placebo (n=91)

Median age (range), years 66 (21-84) 68 (21-82) 67 (21-89) 70 (39-86)

Male/female, % 88/12 88/12 86/14 86/14ECOG PS, %01-2

5149

5347

6040

5644

Region (Europe/North/other), %

86/11/3 87/9/4 93/4/2 87/10/3

Etiology, %Viral hepatitis (HBV/HCV)Alcohol/other

18/2626/30

20/2524/31

20/3727/17

13/3233/22

Child-Pugh class (A/B), % 94/5 99/1 97/3 97/3BCLC stage (B/C), % 0/100 0/100 60/40 56/44MVI (yes/no), % 52/48 58/42 0/100 0/100EHS (yes/no), % 76/24 71/29 0/100 0/100

Adapted from Sherman et al. ASCO 2008, abstract 4584.

SHARP: RECIST Response Stratified by MVI and/or EHS

Percentage of patients

MVI and/or EHS present MVI and/or EHS absent

Sorafenib (n=209)

Placebo (n=212)

Sorafenib (n=90)

Placebo (n=91)

ORR (CR + PR) 2.4 0.9 2.2 0

SD 65.6 62.7 82.2 78.0

PD 21.5 27.4 10.0 16.5

Not assessable 10.5 9.0 5.6 5.5

DCR* 41.2 27.8 48.9 40.7

*Disease control rate is defined as the proportion of patients with a best response of CR, PR or SD by RECIST that is maintained for ≥28 days following demonstration of that response.

Adapted from Sherman et al. ASCO 2008, abstract 4584.