'It is a perfect example of how understanding a patient's genetics and the biology of their tumour can be used to target its weaknesses and personalize treatment,' said Professor Andrew Tutt, director of the Breast Cancer Now Research Centre at The Institute of Cancer Research, London, who was not involved in the study. 'Olaparib is already available for women with BRCA-mutant advanced ovarian cancer, and is the first drug to be approved that is directed against an inherited genetic mutation.'
Olaparib belongs to a class of drugs called PARP-inhibitors that act against proteins involved in DNA repair. Inherited BRCA mutations, which occur in up to three percent of all breast cancers, can impair the normal function of DNA repair by favouring abnormal cell growth, and so increase the risk of cancer.
In the OlumpiAD trial, carried out at the Memorial Sloan Kettering Cancer Center, New York, olaparib was given to 302 women who had metastatic breast cancer caused by BRCA mutations. The treatment led to tumour shrinkage in 60 percent of women, compared with only 29 percent of those treated with standard chemotherapy. After a median follow-up of 14 months, 42 percent of women showed slower cancer progression.
Researchers said the results were too preliminary to state whether patients could really benefit from olaparib treatment in terms of extended life. However, side effects such as hair loss and low white blood cell counts were reduced and only 37 percent of the patients experienced serious side effects compared with 50 percent for chemotherapy, demonstrating a better health-related quality of life.
'This is the first demonstration of improved outcomes with a PARP inhibitor compared to standard treatment in women with BRCA mutation-associated breast cancer,' said lead study author Dr Mark Robson of Memorial Sloan Kettering Cancer Center, New York. 'It is especially encouraging to see that olaparib was effective against triple negative breast cancers that arise in women with inherited, germline BRCA mutations. This type of breast cancer is particularly difficult to treat and often affects younger women.'
The results were published in the New England Journal of Medicine and presented at the 2017 American Society of Clinical Oncology Annual Meeting.
AstraZeneca expects to seek approval for use of the drug in breast cancer toward the end of this year, and two more trials will investigate potential applications of olaparib in patients with other types of breast cancer.