The Lancet Oncology has published data from a Phase 2 clinical trial investigating maintenance monotherapy with AstraZeneca’s investigational oral poly ADP ribose polymerase (PARP) inhibitor olaparib in patients with platinum-sensitive recurrent serous ovarian cancer.
The results of a preplanned retrospective subgroup analysis showed that treatment with olaparib extended progression-free survival (PFS) by 6.9 months for patients with the BRCA mutation (11.2 months vs 4.3 months) compared to placebo.
Ovarian cancer is a serious and life-threatening disease with 7,000 women diagnosed in the UK every year.
Ovarian cancer is the fifth most common cancer among women in the UK and around 4,000 women die from the disease each year in the UK.
There is currently no reliable screening method to detect ovarian cancer and symptoms often go unnoticed or are not thought to be serious.
As a result, 70% of ovarian cancer cases are not diagnosed until the disease has spread beyond the ovaries.
“High-grade serous is the most common, and most aggressive, form of ovarian cancer, and currently patients with the condition face a poor prognosis and limited treatment options,” says Professor Jonathan Ledermann, M.D, Professor of Medical Oncology in the University College London Cancer Institute and lead olaparib trial investigator.
“These results demonstrate that olaparib significantly increased progression-free survival in ovarian cancer patients with the BRCA mutation, supporting its potential use as a targeted therapy in this population.”
The paper reports results of an interim analysis of overall survival and a retrospective, preplanned analysis of data by BRCA mutation status from a randomised, double-blind, phase 2 study that assessed maintenance treatment with olaparib 400 mg twice daily (capsules) versus placebo, in patients with platinum-sensitive recurrent serous ovarian cancer who had received two or more platinum-based regimens and who had a partial or complete response to their most recent platinum-based regimen.
The primary endpoint was PFS, analysed for the overall population and by BRCA status.
PFS in this setting, provides a meaningful evaluation of a treatment effect as it relates to tumour growth, tumour burden and disease progression.
A long PFS in the maintenance setting allows patients more time without chemotherapy treatment.
Seven percent of patients experienced the most common grade 3 or worse events in the olabarib group: fatigue and anaemia.
Serious adverse events were also reported in 18 percent of patients.
Tolerability was similar in patients with mutated BRCA and the overall population.
“There is clearly an unmet need in the treatment of ovarian cancer and these data highlight the potential benefits that olaparib could bring to appropriate patients with the BRCA mutation,” said Dr Catriona McMahon, Medical and Healthcare Affairs Director, AstraZeneca UK and Ireland.
“Olaparib was discovered here in the UK and we are working closely with the regulatory authorities to ensure patient access should it be approved for use in Europe.”
These data formed the basis of a Marketing Authorisation Application for olaparib to the European Medicines Agency on 27th September 2013.
If approved, olaparib has the potential to be a first-in-class PARP for patients with BRCA mutated platinum-sensitive relapsed ovarian cancer.