Two-drug approach could offer hope to ovarian cancer patients

A clinical trial combining two cancer therapies has shown promising results in patients with low grade serous ovarian cancer.

In the Phase 1 study run by the Institute of Cancer Research (ICR) and the Royal Marsden Hospital, both in London, the drug combination prevented patients' cancers from progressing for just under two years on average. Of 24 patients who took part, 46 percent saw their tumours shrink significantly and the proportion was higher (64 percent) in patients with a mutation in the KRAS gene.

'I am delighted that this drug combination has worked so well in a group of patients who are in urgent need of new treatments said Dr Susana Banerjee, research lead for the Royal Marsden's gynaecology unit. 'If these findings are confirmed in larger trials, they'll represent a significant advance in low-grade serous ovarian cancer treatment.'

Low grade serous ovarian cancer is a rare, slow-growing form of the disease. On average it presents in younger patients than other types of ovarian cancer and often responds poorly to chemotherapy and hormone-based treatments.

The two drugs used in the trial are defactinib, a FAK inhibitor and an RAF/MEK inhibitor called VS-6766. Each of these inhibits signalling molecules in pathways associated with cell survival, proliferation and migration.

KRAS is a known oncogene, and mutated variants are found in many cancers. KRAS mutations are difficult to target with drugs, but the RAF/MEK targets are involved in the same pathway. For this reason, MEK inhibitors had already shown promise in treating low grade serous ovarian cancer but tumours would quickly develop resistance.

Adding a FAK inhibitor made it much harder for the tumour to evolve resistance, and the approach was successful even in patients who had been treated with a MEK inhibitor before joining the study.

'Scientists have been working to develop treatments that can effectively target KRAS-driven cancers for decades,' said ICR chief executive Professor Kristian Helin. 'This study has turned a deep understanding of how cancer fuels its growth and develops resistance into a highly targeted treatment for patients who currently have few treatment options.'