New drug combination offers hope to ovarian cancer patients

Thousands of women with ovarian cancer could benefit from a drug combination thought to be nearly twice as effective as the next best treatment.

Scientists hope the results, presented at the world’s largest cancer conference, will lead to a new option for patients with advanced low-grade serous ovarian cancer (LGSOC), a rare form of the disease that has a poor response rate to current treatments.

The international study, led by researchers from The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, has tested avutometinib alone and in combination with defactinib in 29 patients with LGSOC.

Both drugs are designed to block signals that encourage cancer cells to grow.

Approved treatment options available for patients with advanced LGSOC in the UK are currently limited to chemotherapy and hormone therapy, with response rates typically ranging from 0-14 per cent.

According to these results, nearly half (45 per cent) of patients treated with avutometinib in combination with defactinib saw their tumours shrink significantly, suggesting the new combination could be almost twice as effective as the next best treatment.

Responses to the drug combination were particularly promising in those with a mutation in a gene called KRAS, with six in 10 patients experiencing significant tumour shrinkage.

LGSOC accounts for about one in 10 cases of ovarian cancer, with around 700 women in the UK and 80,000 worldwide diagnosed each year. Compared with other forms of the disease, LGSOC tends to affect younger women.

Global lead investigator of the study, Dr Susana Banerjee, consultant medical oncologist and research lead for The Royal Marsden NHS Foundation Trust gynaecology unit, said: “These initial results could be fantastic news for women with low grade serous ovarian cancer, indicating a far more effective option than current treatments may be on the horizon.

“It’s wonderful to see so many patients experience a meaningful response to this innovative drug combination and I’m so grateful to all who joined the trial, making this research possible.

“Low grade serous ovarian cancer does not respond well to currently approved treatments, so these results could represent a significant breakthrough in treating the disease.

“We are hopeful this drug combination will one day become a standard of care for women with low grade serous ovarian cancer.”

Avutometinib is a dual RAF and MEK inhibitor, a type of targeted drug that blocks certain proteins that help control cancer growth and survival. Studies have shown the drug can become ineffective over time as tumours develop resistance to treatment.

However, when combined with defactinib – which is designed to combat a protein that encourages drug resistance – researchers believe avutometinib works more efficiently. The drug combination is over four times more effective than avutometinib alone.

Christine Cull, a 71-year-old from Coventry, was diagnosed with low grade serous ovarian cancer in 2009. She found out the disease had returned in 2014 and she was treated with chemotherapy and hormone therapy, which didn’t work for her, along with several surgeries.

She joined the trial at The Royal Marsden in August 2020 and has been treated with the new drug combination ever since. Her latest scan results showed no evidence of disease.

“My lowest point throughout this experience was in 2019 when my local hospital said there was nothing more they could do for me – it was horrible,” Cull explained.

“My cancer had completely resisted chemotherapy and hormone therapy, and my team weren’t able to operate again.

“Fortunately, my doctor referred me to The Royal Marsden who, as specialist cancer centre, had the expertise to do another surgery. When the disease started growing again the next year, this trial had opened at the hospital, and I was chuffed to be able to join.

“I have scans every three months and each time we’ve seen the cancer getting smaller and smaller. After finding out recently that the cancer is currently not even visible on scans, I felt relieved, amazed and so happy to be able to pass this good news onto family and friends.”

Cull said the hospital gave her and her family hope when she thought all her options had been exhausted.

“The Royal Marsden means so much to me. Because of this trial, I am able to live my life with my husband, three children and three grandchildren with barely any side effects.”