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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

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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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R

Treatment A: Gemcitabine +Carboplatin

Treatment B: Gemcitabine + Carboplatin + BSI-201 (a PARP – inhibitor)

Triple NegativeMBC

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RESULTS

Treatment

A

Treatment

Bp-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 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

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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 PARP-inhibitors will help establish the magnitude of benefit and their role for early stage and advanced TN breast cancer