New drug for inherited breast and ovarian cancers shows promise in early trials
Olaparib, a new type of experimental drug called a PARP inhibitor, has shown promising results against inherited forms of breast and ovarian cancer in two small clinical trials led by scientists at the Breakthrough Breast Cancer Research Unit at King's College London.
The drug specifically targets cancers caused by faulty BRCA1 or BRCA2 genes. Women carrying these inherited genetic faults have a greatly increased risk of breast and ovarian cancers, and the mutations are thought to cause about two to five per cent of all breast cancers and about five to 15 per cent of ovarian cancers.
The new drug blocks a protein called 'poly(ADP-ribose) polymerase' (PARP), causing cancer cells with a BRCA fault to lose the ability to repair damage to their DNA. Because the cancer cells are already faulty, this extra problem kills them.
Olaparib is a targeted form of treatment, meaning it has been designed to kill cancer cells while leaving healthy cells unharmed.
This week the results of two early clinical trials of olaparib were published in the Lancet medical journal. The international trials focused on breast and ovarian cancers in women with BRCA faults.
In the first trial, scientists looked at 54 women with advanced breast cancer, all of whom had previously been treated with chemotherapy.
Half of the women were given 100mg doses of olaparib, while the other half received 400mg doses.
In the group taking the higher dose, over 40 per cent of tumours shrank significantly and tumours typically did not grow any larger for nearly six months.
In the second trial, 57 women with ovarian cancer were recruited, all of whom had previously received chemotherapy.
Of these, 24 took 100mg doses of olaparib while the other 33 were given 400mg doses.
Researchers found that more than one-third of tumours in the higher-dose group shrank significantly.
The trials were led by Dr Andrew Tutt, consultant clinical oncologist and director of the Breakthrough Breast Cancer Research Unit at King's College London.
He said: "This new type of treatment is showing great promise for patients whose cancer is caused by this specific genetic fault. It was remarkable to see that olaparib benefited women with advanced breast and ovarian cancer who had already been treated with several different chemotherapy drugs.
"However, it is important to remember this drug is at an early stage of development, and further clinical trials will be required to fully evaluate its potential before it would be considered as a licensed treatment."
Dr Susan Domchek, an associate professor of medicine at the University of Pennsylvania who was involved in the breast cancer trial, commented: "This is a different way of looking at cancer therapeutics.
"In oncology, this is really one of the first times that we've seen drugs being developed on the basis of inherited susceptibility - and that may open up a whole new avenue of drug development."
Nell Barrie, science information officer at Cancer Research UK, said: "The work of Cancer Research UK scientists has been instrumental in the development of PARP inhibitors.
"This small study is part of the important process of testing the safety and effectiveness of these exciting new drugs, but we'll have to wait for the results of much larger trials to know if PARP inhibitors can help to save lives."
- Audeh, M.,et al (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial The Lancet DOI: 10.1016/S0140-6736(10)60893-8
- Tutt, A. et al. (2010). Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial The Lancet DOI: 10.1016/S0140-6736(10)60892-6