Promising results for new treatment

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, based at Guy’s Hospital in London.

The drug investigated in the trials, olaparib, is one of a new class of drugs called PARP inhibitors and comes in pill form. It targets cancer cells caused by faulty BRCA1 or BRCA2 genes, which affects around 1,500 of the nearly 46,000 women diagnosed with breast cancer in the UK each year. While this is a small group of patients these drugs have been shown in laboratory research to have potential benefits for a wider range of cancer types which share similar characteristics.

The results are for two separate Phase II international, multi-centre clinical trials – one for breast cancer and one for ovarian cancer patients. Both used olaparib and were funded by AstraZeneca, the pharmaceutical company which owns the drug.

The breast cancer trial looked at a group of 54 women with advanced breast cancer who had already received chemotherapy. Twenty seven patients took 100 mg doses of olaparib with another 27 who took 400 mg doses. Over 40% of tumours in the higher dose group reduced significantly in size, and tumours were prevented from progressing for an average of six months.

The ovarian cancer trial looked at a group of 57 women with advanced ovarian cancer who had already received chemotherapy. Twenty four patients took 100 mg doses of olaparib with another 33 who took 400 mg doses. Over 33% of tumours in the higher dose group reduced significantly in size, and tumours were prevented from progressing for an average of six months. For both trials, most patients had only relatively minor side effects, such as fatigue and nausea.

Breast cancer study leader Dr Andrew Tutt, Director of the Breakthrough Breast Cancer Research Unit at King’s College London, 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.”

Olaparib uses the synthetic lethality approach to kill cancer cells with a faulty BRCA1 or BRCA2 gene. It does this by blocking a protein called PARP and is therefore known as a PARP inhibitor. Olaparib causes cancer cells with a BRCA fault to lose control of their DNA stability. This causes the cancer cell to die and means that the tumour should either stop growing or get smaller. Due to the drug working in a targeted way, it kills cancer cells while leaving healthy cells relatively unaffected, which means fewer side effects for patients.

The initial research into a potential targeted treatment for breast cancers with BRCA1 and BRCA2 faults was carried out by Professor Alan Ashworth at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research in London funded by Breakthrough and Cancer Research UK.  Professor Alan Ashworth’s team that included Dr Tutt discovered a very specific DNA repair weakness of these tumours which can be exploited by olaparib. This research enabled the further investigation of olaparib in the current clinical trials as a potential treatment for patients with this type of hereditary breast and ovarian cancer.

Dr Norman Freshney, Director of Research Management at Breakthrough Breast Cancer, said:

“These trial results show the future of personalised medicine by treating cancers according to their genetic faults rather than where they are in the body. This means these drugs could have potential across a wider range of cancer types which share similar characteristics.

“It is encouraging to see findings made in our labs benefiting patients quickly. We now hope to see this work taken further to see if PARP inhibitors could become an option for women whose breast cancer is caused by this genetic fault.”

Hereditary Breast Cancer