Promising early results from drug trial for inherited ovarian cancer

In collaboration with Adfero

A team of UK scientists, part-funded by Cancer Research UK, have found that a new type of drug could help women with an inherited form of ovarian cancer.

Treatment options are limited for the disease, and only four out of ten women currently survive for five years or more.

While patients commonly respond well to surgery and chemotherapy to begin with, the cancer can become resistant to treatment and come back.

Now, early trial results published in the Journal of Clinical Oncology suggest that an experimental drug called olaparib may help to shrink tumours or prevent further tumour growth in around half of ovarian cancer patients who have inherited faults, or mutations, in their BRCA1 or BRCA2 genes.

Inherited BRCA mutations are found in up to 15 out of every 100 breast and ovarian cancers.

Olaparib is a new type of drug called a PARP inhibitor, which works by preventing DNA repair in cancer cells with BRCA gene faults. The cancer cells are unable to repair themselves, so they die.

The drug is being investigated by scientists at The Institute of Cancer Research (ICR) and the Royal Marsden Hospital, who are working with the company KuDOS Pharmaceuticals.

Researchers recruited about 50 ovarian cancer patients with confirmed or suspected BRCA1 or BRCA2 mutations, all of whom had previously been treated with platinum-based chemotherapy drugs.

Patients were grouped according to how well their tumours responded to the platinum drugs. Patients whose cancer came back more than six months after they had been treated with a platinum-based drug were described as having 'platinum-sensitive disease', while those whose cancers came back sooner, or didn't respond at all to platinum treatment, were classed as 'platinum resistant' or 'platinum refractory'.

Patients on the trial began taking olaparib between 2005 and 2008. Twenty of the patients saw their tumours shrink or recorded a significant fall in their levels of CA125, a molecule produced by ovarian cancers. And a further three patients showed no change - either growth or shrinking - in the size of their tumours.

Nine of the 13 patients (70 per cent) with platinum-sensitive cancers showed a response to olaparib. And ten out of 24 patients (41 per cent) with platinum-resistant tumours also responded to the drug.

Women typically responded to olaparib for an average of seven months and a number of patients kept getting benefit from the drug for nearly two years.

The researchers also found that the side-effects tended to be mild in comparison to existing chemotherapy treatments.

Professor Stan Kaye, a Cancer Research UK-funded scientist who is head of the ICR's Section of Medicine and head of the Drug Development Unit at the Royal Marsden Hospital, explained: "There is an urgent need to find new drugs for women diagnosed with ovarian cancer.

"Olaparib is still in early-stage testing but the results so far are very encouraging. These findings raise the possibility that carefully selected patients in future may well be offered olaparib as an alternative to chemotherapy during the course of their treatment."

Professor Kaye added: "We have good reason for thinking that the benefit seen with olaparib in BRCA mutation-linked ovarian cancer may well extend to a broader population of patients with this disease."

Scientists are now carrying out larger trials of olaparib, and the results are expected later this year.

References

  • Peter C. Fong et al. Poly(ADP)-Ribose Polymerase Inhibition: Frequent Durable Responses in BRCA Carrier Ovarian Cancer Correlating With Platinum-Free Interval Journal of Clinical Oncology, 10.1200/JCO.2009.26.9589