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Ovarian cancer drug developed with University of Cambridge research can now be used in combination





An ovarian cancer drug developed thanks to research by Professor Steve Jackson and his team at the University of Cambridge can now be used in a new combination that could help 1,100 women in England.

NICE (National Institute for Health and Care Excellence) has approved the use of olaparib in combination with bevacizumab to help women with certain forms of newly-diagnosed advanced ovarian cancer.

Prof Steve Jackson, of The Gurdon Institute at the University of Cambridge
Prof Steve Jackson, of The Gurdon Institute at the University of Cambridge

In clinical trials the combination therapy increased the length of time patients live before the disease progresses by more than three years - an average of 37.2 months, compared to 17.7 months for those who received bevacizumab with a placebo.

The trial data was unclear on whether the combination increased overall survival, so NICE could not recommend it at this stage for routine NHS use. Instead, it is offering it via the Cancer Drugs Fund, which will allow more evidence to be collected.

Olaparib, which is sold by Cambridge-based AstraZeneca and MSD under the brand Lynparza, was the first PARP inhibitor to be approved and followed pioneering research in Cambridge.

PARP is short for poly (ADP-ribose) polymerase, and is a protein that helps damaged cells to repair themselves. Some cancers rely on PARP to maintain their DNA. By preventing PARP from working, olaparib prevents this DNA damage repair, which causes the cancer cells to die.

Prof Jackson, who is professor of biology and head of Cancer Research UK Laboratories at the Gurdon Institute, University of Cambridge, said: “I am delighted by this decision from NICE which will allow many more women in England to benefit from this personalised medicine.

“Fundamental academic research by my team at Cambridge University led to the concept of PARP inhibition to destroy cancer cells and the development of olaparib, which is now benefiting people with cancer in the UK and in many other parts of the world.

“This is a proud moment for me and the team, and is testament to the important role of UK life sciences in developing transformative new medicines.”

Prof Jackson founded KuDOS Pharmaceuticals in 1997 to translate his team’s DNA damage response work into drugs, the most advanced of which is olaparib. KuDOS was acquired by AstraZeneca in 2006 and olaparib/ Lynparza has now benefitted tens of thousands of patients around the world with ovarian, breast, prostate and pancreatic cancers.

Oncologist Dr Susana Banerjee, of The Institute of Cancer Research, said it “spearheaded the introduction of personalised treatment of advanced ovarian cancer in the UK and around the world”.

Prof Steve Jackson, of The Gurdon Institute at the University of Cambridge
Prof Steve Jackson, of The Gurdon Institute at the University of Cambridge

The drug exhibits cytotoxicity towards cancer cells mutated in the BRCA1 or BRCA2 genes, but only has mild effects on normal cells.

This is thanks to a mechanism termed synthetic lethality - which describes how mutations in two genes lead to cell death, but a mutation in either one on its own does not.

Bevacizumab, meanwhile, is a recombinant humanised monoclonal antibody, sold under the brand name Avastin by Roche.

It targets vascular endothelial growth factor (VEGF), a protein that helps cancers to grow blood vessels so they can get nutrition and oxygen from the blood to survive and grow. Known as an anti angiogenesis treatment, bevacizumab blocks this protein, effectively starving the cancer cells.

The combination of these two drugs is available for women whose cancer has had a complete or partial response after first-line treatment with platinum-based chemotherapy and bevacizumab. The cancer must also test positive for homologous recombination deficiency (HRD)

Nearly half (48 per cent) of women with newly-diagnosed advanced ovarian cancer have HRD-positive tumours. A new genomic HRD test will be introduced in England on the NHS for the first time to support the new treatment combination.

“It is now essential that patients are offered the HRD test at diagnosis,” stressed Dr Banerjee.

Until now, ovarian cancer patients without a mutation in the BRCA genes have had to wait until their cancer has returned, when the prognosis is worse, to get access to a PARP inhibitor treatment. But under NICE’s new recommendation, patients with HRD are eligible, regardless of their BRCA status.

Annwen Jones, chief executive of Target Ovarian Cancer, said: “This announcement is an extremely positive sign of the progress we’re now making in ovarian cancer treatment. The NICE recommendation and the introduction of HRD testing means that so many more women will receive treatment personalised to them. The future we want to see – where every woman with ovarian cancer has access to innovative treatments – has come a big step closer.”

Arun Krishna, head of oncology at AstraZeneca UK, said: “Olaparib has its scientific grassroots in laboratories across the UK and so it is especially welcome news that significantly more women in England will now have the chance to benefit from this new treatment regimen.

“We have come a long way in treating ovarian cancer with genomic profiling enabling the identification of subtypes of disease, which we can then target with appropriate treatment.

“Our focus now is on working closely with external partners and the Genomic Laboratory Hubs to introduce and fund the first-ever HRD testing service in England.”

David Long, UK oncology business unit director, MSD, said: “Ovarian cancer has the worst prognosis and highest death rate among all gynaecological cancers, and advances in treatment are key to changing this story. From today, more women will have the chance to benefit from this personalised treatment regimen that could change the course of their disease, with data showing that disease progression could be stalled for more than three years. It’s now crucial that every woman in England who could possibly benefit from this treatment combination is offered an HRD test.”

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