Olaparib to be Trialled for Advanced Ovarian Cancer Treatment
Having previously discontinued its development several years ago, AstraZeneca have completed a full U-turn by announcing their intention to move Olaparib into Phase III trials. The news comes after a retrospective analysis of the Phase II trial data was carried out.
Although the analysis was unable to demonstrate a significant overall survival benefit, it is hoped that the Phase III trial will produce a large progression-free survival benefit and that this will be enough for Olaparib to gain approval from regulatory authorities.
The data was presented at the annual meeting of the American Society of Clinical Oncology (ASCO) on 1 June 2013. In its analysis, AstraZeneca found that Olaparib may be an effective treatment for patients suffering from advanced ovarian cancer with BRCA1/2 mutations.
Previous analysis of Phase II trial data back in 2011 had concluded that the progression-free survival benefit was unlikely to produce a change in overall survival. As a result, the group had initially decided to halt Olaparib's development.
How Olaparib Works
The reason Olaparib may be effective in treating certain ovarian cancer patients is because tumor cells with BRCA1/2 mutations rely heavily on an enzyme called PARP to repair damaged DNA.
Olaparib is a PARP inhibitors, which means that it blocks the enzymatic activity of PARP or causes PARP to accumulate on DNA; a process known as 'PARP blocking.'
As a result, Olaparib is able to kill BRCA1- or BRCA2-deficient cells.
Phase II Trial
The Phase II trial consisted of a randomised, placebo-controlled study, designed to assess the safety of the drug and its efficiency as a maintenance monotherapy for women with platinum-sensitive ovarian cancer. All of the women had already received chemotherapy.
Patients involved in the trial either received daily 400mg dose of Olaparib or they received a placebo.
Retrospective analysis found that, amongst BRCAm patients, Olaparib treatment produced a reduced risk of 82% in disease progression or death and produced a median progression-free survival benefit of 11.2 months, compared to the 4.3 months associated with the placebo treatment.
AstraZeneca's research is geared towards using Olaparib as a potential maintenance therapy.
If it is given approval after Phase III trials, Olaparib could be given to ovarian cancer patients who have previously received platinum-based chemotherapy and have demonstrated remission.