www.OncologyEducation.ca 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 22 nd , 2009
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Authors: Dr. Sunil Verma Date posted: June 22 nd , 2009
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 22 nd , 2009. Background. - PowerPoint PPT Presentation
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www.OncologyEducation.ca
Efficacy of BSI-201, a PARP-Inhibitor in combination with Gemcitabine/Carboplatin in Triple Negative Breast Cancer:
Randomized Phase II trialPresented by Dr. Joyce O’Shaughnessey
Authors: Dr. Sunil Verma
Date posted: June 22nd, 2009
www.OncologyEducation.ca
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
• This is an important study as it shows that the addition of PARP-inhibitors 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?
TNNon-TN
- What are the long-term toxicities associated with these agents?
? Increase risk of tumorogenesis- Oral vs. IV
www.OncologyEducation.ca
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 PARP-inhibitors will help establish the magnitude of benefit and their role for early stage and advanced TN breast cancer