Cancer treatment selection

PARP inhibitors are a type of drug used in cancer treatment that work by blocking the activity of the PARP DNA repair enzyme. Treatment with PARP inhibitors leads to DNA damage, due to trapping of PARP on the DNA. If this damage cannot be repaired, then this can lead to the death of the cancer cells. PARP inhibitors are approved for the treatment of some ovarian, breast and pancreatic cancers and have significantly improved outcomes for patients.

PARP inhibitors have been shown to be effective against tumours that have deficient homologous recombination repair processes. Therefore, before a PARP inhibitor can be prescribed, a patient’s cancer is first tested for certain genetic defects that predict whether this DNA repair pathway is defective — either the BRCA1 or BRCA2 mutation, or homologous repair defects (HRD). If the test is positive (the repair pathway defects are present) then the patient can be prescribed a PARP inhibitor. In this setting, the response rate to treatment is approximately 30 per cent.

The challenge with PARP inhibitors is that the test for BRCA1/2 mutations or HRD is positive in only a relatively small number of cancers — approximately 10 per cent of breast cancers, 20–30 per cent of ovarian cancers and one per cent of lung cancers — meaning only a small number of patients can be treated with PARP inhibitors. However, PARP inhibitors have shown benefit among the larger group of patients that do not have a positive BRCA1/2 mutation or HRD test. Currently, these patients are not able to be treated with PARP inhibitors.

CVP002 is being developed to identify patients who are likely to respond to PARP inhibitor therapy, separate to testing for BRCA1/2 mutations or HRD. This will enable more patients with ovarian, breast and pancreatic cancers to access these important cancer treatments and improve outcomes for patients.