Experimental drug shrinks tumours in women with hereditary breast and ovarian cancers

In collaboration with Adfero

An experimental drug called olaparib has been shown to shrink tumours in women whose advanced cancers were caused by faults in their BRCA genes.

The international phase-II studies, both published in the Lancet, looked at women with advanced ovarian or breast tumours.

Their results add further weight to the idea that the key to treating certain types of cancer may be to target their underlying genetic weaknesses, rather than the organ in which the cancer originated.

First author on the ovarian trial Dr William Audeh, a cancer expert specialising in cancer genetics at Cedars-Sinai Medical Centre in the US, described the findings as "significant".

He revealed: "Olaparib is the first single-agent, non-chemotherapy treatment to show benefit to patients with cancers that result from BRCA1 or BRCA2 gene mutations.

"Until now, treatments for cancer have been selected based upon where in the body the cancer originated. [This study suggests] that it is the underlying genetic weakness of a cancer, not the organ of origin, that is the key to selecting effective therapy."

The investigational drug olaparib is a poly-ADP-ribose phosphorylase (PARP) inhibitor.

It is designed to interfere with an enzyme called poly-ADP ribose-phosphorylase, or PARP, which helps to repair DNA damage caused to cancer cells.

Tumours which are caused by faults in BRCA genes already have difficulty repairing their DNA, for example when given chemotherapy.

By blocking the activity of PARP, olaparib in theory makes the chemotherapy much more effective.

The ovarian cancer study, which was coordinated by researchers at the Breakthrough Breast Cancer Research Unit at King's College London, as well as researchers in the US and Australia, involved 57 patients, 33 of whom were given a high dose of olaparib.

Eleven of these women saw a significant reduction in the size of their tumours. Three out of 24 women given a lower dose also benefited.

In the breast cancer trial, 27 women received the higher dose, of whom 11 responded, while six out of a further 27 women given a lower dose also responded.

Side-effects tended to be relatively mild and included nausea, fatigue and anaemia.

Dr Audeh noted that many women with advanced BRCA-mutated cancer have limited treatment options, as they will have already tried several different chemotherapy drugs.

He revealed: "PARP inhibitors may be a promising new option for this heavily 'pre-treated' population."

Dr Claire Knight, health information officer at Cancer Research UK, said: "PARP inhibitors have been showing excellent promise in early clinical trials and these results are also encouraging.

"Cancer Research UK scientists have been key players in developing this new generation of cancer drugs. We look forward to the results of larger clinical trials to determine if these drugs could be an effective way to treat cancers caused by faults in the BRCA genes."

References

  • 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, 376 (9737), 235-244 DOI: 10.1016/S0140-6736(10)60892-6
  • 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, 376 (9737), 245-251 DOI: 10.1016/S0140-6736(10)60893-8