New drug combination twice as effective for some ovarian cancer patients as next best treatment
Findings suggest new hope for patients suffering with disease that has a poor response rate to current treatments.
A targeted drug combination for patients with a type of ovarian cancer could be nearly twice as effective as the next best treatment, according to interim results from a Phase 2 study.
The international RAMP-201 study, has been led by researchers from The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, and sponsored by Verastem Oncology. The study has tested avutometinib alone and in combination with defactinib in 29 patients with low-grade serous ovarian cancer (LGSOC). Both drugs are designed to block signals that encourage cancer cells to grow.
Researchers hope these results, which are being presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, will lead to a new option for patients with advanced LGSOC, a rare form of the disease that has a poor response rate to current treatments.
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. Alongside standard treatment, LGSOC patients in England can access trametinib, a targeted treatment, via the Cancer Drug Fund, which has a response rate of 26 per cent.
Improvement on current treatments
According to the study’s interim 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 (60 per cent) patients experiencing significant tumour shrinkage. However, nearly a third (29 per cent) of patients without the mutation also had an encouraging response, which is also an improvement on standard treatment.
Patients previously treated with other types of targeted therapies, including MEK inhibitors, also saw their tumours shrink following treatment with the drug combination.
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. This is confirmed by these results, which demonstrate that the drug combination is over four times more effective than avutometinib alone.
RAMP-201 follows the phase 1 FRAME trial, which tested avutometinib (then known as VS-6766) and defactinib on a slightly smaller cohort of patients with advanced LGSOC and was led by researchers from the Oak Foundation Drug Development Unit at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London. While survival data is not yet available from RAMP-201, results from FRAME indicate that this patient group lives an average of 23 months following treatment with this drug combination before their cancer progresses.
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 and Team Leader in Women’s Cancers at The Institute of Cancer Research, London, 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.”
