AstraZeneca has announced that the National Institute for Health and Care Excellence (NICE) has issued Technology Appraisal Guidance (TAG) for LYNPARZA® (olaparib), recommending it as a cost effective option for women with platinum-sensitive relapsed (PSR) BRCA-mutated (BRCAm) high-grade serous ovarian cancer who have had three or more courses of platinum-based chemotherapy.1 Clinical commissioning groups, NHS England and local authorities are required to comply with this recommendation and ensure that olaparib treatment is funded and accessible within 90 days.
Ovarian cancer is a serious and life-threatening condition that causes more than 4,000 women in the UK to die each year.2 The UK's survival rate for ovarian cancer lags behind other major European countries with England having the lowest five year survival rate in Europe.3 Up to 21% of women with the most aggressive form of ovarian cancer have the genetic BRCA mutation and it is this patient group for whom olaparib is licensed in Europe. The only other treatment options are chemotherapy or surgery.4
NICE has recommended use of olaparib in patients who have completed three or more courses of platinum based chemotherapy and who meet the European license criteria. Olaparib is the first targeted therapy for women with BRCAm ovarian cancer and clinical trials show that it provides an important quality of life benefit by significantly increasing the time it takes for the disease to progress and the time to further chemotherapy cycles. There was an 82% risk reduction in time to progression versus standard 'watch and wait', which is the largest ever effect for this outcome in women with ovarian cancer (HR 0.18, p<0.0001; median progression free survival, 11.2 months versus 4.3 months).5 These data are for the overall population that olaparib is licensed for; data for the NICE-approved patient group are consistent with this.
Professor Jonathan Ledermann, Professor of Medical Oncology at the University College London Cancer Institute and Primary Investigator of the pivotal olaparib clinical trial said: "The positive NICE guidance for olaparib represents a turning point for how women with ovarian cancer and a BRCA mutation are treated by the NHS in England. These patients with recurrent ovarian cancer tend to have a poor prognosis and until now their treatment options have been limited to conventional chemotherapy and surgery. I urge NHS England to implement this guidance immediately as there are many patients who are waiting for treatment and who could benefit significantly."
Greg Rossi, Oncology Business Unit Head at AstraZeneca UK said: "AstraZeneca is delighted that NHS patients in England will soon have access to the first targeted therapy for ovarian cancer. Olaparib is a product of the British science community and it is only right that patients in this country should have the opportunity to benefit from treatment. We hope that NHS England will issue its commissioning policy as soon as possible to allow funding and rapid patient access to olaparib."
To date, the most common side-effects experienced by patients taking olaparib were mild to moderate, did not cause the patient to stop taking treatment, and included nausea, fatigue, vomiting and anaemia.5
The European Commission approved olaparib on 16 December 2014 for platinum-sensitive relapsed (PSR) BRCA mutated (BRCAm) ovarian cancer (including fallopian tube or primary peritoneal) who are in response (complete response or partial response) to platinum-based chemotherapy.6 Olaparib is an innovative, first-in-class oral poly ADP ribose polymerase (PARP) inhibitor which has been evaluated in Phase II studies in serous ovarian cancer patients.1
Olaparib, which is taken in a tablet form, is the first and only targeted therapy for ovarian cancer and offers a new approach to the way the disease is treated.1 It works by blocking one of the cancer cell's repair pathways, and in patients who also have the BRCA mutation, this results in the cancer cell dying.
For women with a BRCA gene mutation, their risk of ovarian cancer is as high as 40-60 percent, compared to a two percent risk in the general female population.7 There are approximately 1,100 women per year in England and Wales who are diagnosed with BRCAm ovarian cancer, including around 450 women who have had three or more courses of platinum-based chemotherapy who could be eligible for treatment with olaparib through the NHS.8
The summary of product characteristics for olaparib can be accessed at: https://www.medicines.org.uk/emc/medicine/30359.
About PARP inhibitors
DNA is fragile and it is estimated that tens of thousands of DNA breaks occur every day in an active cell. There are a number of different proteins (e.g. PARP1 and PARP2) that are involved in the repair of DNA strand breaks.9
Olaparib is known as a PARP inhibitor as it induces cell death by blocking the PARP repair pathway and prevents the PARP proteins from repairing DNA breaks.10 Several other cell repair pathways exist to compensate for these occurrences. Genes known as BRCA1 and BRCA2 are involved in one of these alternative repair pathways and, in normal cells, DNA can be repaired.11
However, in cancer cells with certain genetic mutations in DNA repair pathways, such as BRCA mutations, these alternative repair pathways fail to work, and following PARP inhibitor treatment - the cell dies.11,12