Transcript PFS/TTP (median, mos)

Efficacy of BSI-201, a PARP-Inhibitor in combination with
Gemcitabine/Carboplatin in Triple Negative Breast Cancer:
Randomized Phase II trial
Presented by Dr. Joyce O’Shaughnessey
Authors: Dr. Sunil Verma
Date posted: June 22nd, 2009
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Background
• Triple Negative (TN) disease represents the next frontier
in Breast Cancer
• TN disease shares key features with Basal-like and
BRCA associated cancer
– BRCA dysfunction
– Susceptibility to DNA damaging agents
• In the setting of BRCA dysfunction, the cancer cell
increasingly relies on PARP for DNA repair process
– This may represent an important therapeutic target
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Treatment A: Gemcitabine +Carboplatin
R
Triple Negative
MBC
Treatment B: Gemcitabine + Carboplatin
+ BSI-201 (a PARP – inhibitor)
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RESULTS
Treatment
A
Treatment
B
p-value
Response
Rate (%)
16%
48%
0.002
PFS/TTP
(median,
mos)
3.3 m
6.9 m
<0.0001
OS
(median,
mos)
5.7 m
9.2 m
0.0005
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STUDY COMMENTARY
• This is an important study as it shows that the addition of PARPinhibitors to chemotherapy improves the outcome for TN MBC
• This is the first Phase II trial evaluating this class of drugs in MBC
• There is a planned Phase III trial designed to evaluate BSI-201 in
combination with carboplatin+gemcitabine
• There are some unanswered questions related to this class of drugs:
- Do PARP-Inhibitors need DNA damaging stimulus?
-Will they be effective in a broader subgroup of patients?
TN
Non-TN
- What are the long-term toxicities associated with these
agents?
? Increase risk of tumorogenesis
- Oral vs. IV
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BOTTOM LINE FOR CANADIAN MEDICAL
ONCOLOGISTS
• Triple Negative Breast Cancer is associated with poor prognosis and
represents an aggressive phenotype of breast cancer.
• Majority of TN disease is associated with basal-like profile.
Furthermore, basal-like breast cancer shares a number of features
associated with BRCA related cancers
• TN breast cancer may particularly be sensitive to DNA damaging
agents including Cisplatin and PARP inhibitors
• This study suggests that PARP inhibitors are efficacious for TN MBC
• While the results from this Phase II trial are impressive, there are still
a number of unanswered questions and future trials evaluating PARPinhibitors will help establish the magnitude of benefit and their role for
early stage and advanced TN breast cancer
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