Treatment 6 cycles of: Doxorubicin 60 mg/m 2 IV* Day 1 in 21-day cycles Sorafenib 400 mg po bid
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Transcript of Treatment 6 cycles of: Doxorubicin 60 mg/m 2 IV* Day 1 in 21-day cycles Sorafenib 400 mg po bid
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Final Results From a Phase II, Randomized, Double-blind Study of Sorafenib Plus Doxorubicin Versus Placebo Plus
Doxorubicin in Patients With Advanced Hepatocellular Carcinoma
Authors: Abou-Alfa GK, Johnson P, Knox J, Davidenko I, Lacava J, Leung T, Mori A, Leberre M-A, Voliotis D, & Saltz LB
Date posted: October 22, 2007
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R
Treatment 6 cycles of:•Doxorubicin 60 mg/m2 IV* Day 1 in 21-day cycles•Sorafenib 400 mg po bid
Then Sorafenib 400 mg po bid
Treatment 6 cycles of:•Doxorubicin 60 mg/m2 IV* Day 1 in 21-day cycles•Placebo 2 tablets po bid
Then Placebo 2 tablets po bid
Advanced
Hepatocellular CA
• ECOG 0-2
• Child’s Pugh A
• No Previous
Chemoembolization
N= 96
Primary Outcome: TTP
Randomized Phase II Study
* In approved circumstances , doxorubicin doses of up to 450 mg/m2 allowed
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RESULTS - Demographics
DXR/sorafenib (n=47)
DXR/placebo (n=49)
Gender n (%) Male 31 (66) 42 (86)
Female 16 (34) 7 (14)
Age (years) Mean 63 62
ECOG n (%) 0 22 (47) 16 (33)
1 18 (38) 25 (51)
2/3 4 (9) 4 (8)
Missing 4 (9) 4 (8)
Child’s Pugh n (%) A 47 (100) 48 (98)
B 0 (0) 1 (2)
Extrahepatic disease n (%) Yes 24 (51) 32 (65)
No 23 (49) 17 (35)
Macroscopic Vascular Invasion n (%)
Yes 13 (28) 16 (33)
No 33 (70) 32 (65)
Missing 1 (2) 1 (2)
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RESULTS
• Considering the interim results of the Phase III SHARP trial
(sorafenib vs placebo), an Independent Data Monitoring Committee (DMC) performed an interim analysis in January 2007
• “DMC would advise the sponsor to consider discontinuation of this Phase II trial”
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RESULTS
Adria/
Sorafenib
Adria/
PlaceboP Value
Response Rate (%)
4% 2%
Stable Disease
77% 55%
TTP (median,
mos)8.6 4.8
HR 0.6
P=0.076
PFS (median,
mos) 6.9 2.8
HR 0.57
P=0.012
OS
(median, mos)
13.7 6.5HR=0.45
P=0.0049
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TOXICITY
Adria/
Sorafenib
Gr 3/4
Adria/
Placebo
Gr 3/4
Diarrhea 11% 10%
Febrile Neutropenia
4% 10%
Hand Foot
Syndrome9% 0
LV Dysfunction
2% 0
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STUDY COMMENTARY
• This randomized phase II trial demonstrated a statistically and clinically significant survival benefit for adriamycin and sorafenib vs adriamycin and placebo
• Coupled with the SHARP trial (Sorafenib vs Placebo - Llovet, ASCO 2007) supports growing body of evidence for sorafenib in HCC
• Larger trials necessary to determine optimal role of adriamycin/sorafenib in HCC
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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS
• Sorafenib and adriamycin and sorafenib as a single agent could be considered for use in patients with HCC who are candidates for systemic therapy
•Cost and reimbursement of sorafenib may limit its widespread use in Canada