Transcript Slide 1

A randomized phase II/III trial of a tumor vascular
disrupting agent fosbretabulin tromethamine (CA4P)
with carboplatin and paclitaxel in anaplastic thyroid
cancer (ATC): Final survival analysis for the FACT trial
Authors: Sosa J, Elisei R, Jarzab B, Bal C, Koussis H, Gramza A, Ben-Yosef R, Gitlitz B,
Haugen B, Karandikar S, Khuri F, Licitra L, Remick S, Marur S, Lu C, Ondrey F, Lu S and J
Balkissoon
Reviewed by Dr. Stephanie Snow
ASCO 2011 abstract 5502 Oral Session June 6, 2011
Date posted: June 2011
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STUDY BACKGROUND
• ATC is a rare, highly lethal form of thyroid cancer:
– Median survival from diagnosis 3-9 months
– 1 year survival <10%
• Very few effective treatment options: none have
improved OS in patients with advanced disease
• Chemotherapies with activity in ATC include
doxorubicin, platinums and taxanes
• CA4P:
– Small molecule pro-drug of a cytotoxic naturally occurring in
the willow tree
– Selectively disrupts tumor blood vessels by destabilizing
endothelial cell microtubules
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Study Design
n = 80
Primary
Outcome:
Overall Survival
R
2:1
ATC
ECOG PS ≤ 2
Treatment A:
CA4P 60mg/m2 IV d1,8,15 q21d x 6
Carboplatin AUC 6 IV d2 q21d x 6
Paclitaxel 200 mg/m2 IV d2 q21 d x 6,
then maintenance CA4P 60mg/m2 IV d1,8 q21d
until disease progression or drug toxicity
Treatment B:
Carboplatin AUC 6 IV d1 q21d x 6
Paclitaxel 200 mg/m2 IV d1 q21 d x 6
Allowed previous
lines of treatment
Life expectancy
≥ 12 weeks
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RESULTS
Treatment
A
Treatment
B
p-value
Median
Survival
(months)
5.2
4.0
NS
1 year
OS (%)
25.5
8.7
NS
Trial closed at 80 patients due to unsustainably low accrual – target
enrolment was 180 patients
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TOXICITY
Treatment
A
All
Treatment
A
Gr 3/4
Treatment
B
All
Treatment
B
Gr 3/4
Hypertension
36%
4%
4%
4%
QTc
Prolongation
16%
4%
0%
0%
Myocardial
Ischemia
4%
0%
0%
0%
Pulmonary
Embolus
2%
2%
4%
0%
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TOXICITY
Treatment
A
All
Treatment
A
Gr 3/4
Treatment
B
All
Treatment
B
Gr 3/4
Neutropenia
59%
45%
25%
12%
Febrile
Neutropenia
6%
6%
9%
9%
Thrombocytopenia
16%
4%
0%
0%
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STUDY COMMENTARY
• This trial closed early due to difficulties accruing
enough patients, despite being open in 40 sites
in 11 countries:
– Rare disease
– Patients often too ill to travel for treatment
– 31 patients died after signing consent but waiting to
be randomized
• This may have led to the trial being
underpowered to detect survival differences
• There were, however, trends suggesting that
CA4P has activity in this disease with few other
treatment options
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STUDY COMMENTARY
• A larger relative benefit was seen in 1 year
survival as opposed to median overall survival
• This may imply that there is a subgroup which
benefits for a longer period of time, creating a
“tail effect” on the survival curve
• Preplanned subset analysis were performed:
– Analysis limited to subjects age ≤ 60 (n=35):
• Median survival 10.6 vs 3.1 months, HR 0.38 (95% CI 0.17-0.85)
– Analysis limited to subjects with tumor size > 6cm
(n=41):
• Median survival 5.7 vs 3.9 months, HR 0.71 (95% CI 0.33-1.53)
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BOTTOM LINE FOR
CANADIAN MEDICAL ONCOLOGISTS
• This is not a drug ready for prime time yet, but it
is promising to hear about a drug with
manageable side effects that may have activity
in ATC
• Randomized phase III FACT 2 trial is planned
with same design and target n=230 - plan to use
Bayesian Adaptive Design appropriate for
studying a rare disease
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