New drug combination twice as effective for some ovarian cancer patients

Cancer research lab

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 II study.

Researchers hope these results, which were presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, 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 RAMP-201 study, led by researchers from The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, UK, and sponsored by Verastem Oncology, tested avutometinib alone and in combination with defactinib in 29 patients with LGSOC.

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%.

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%.

RAMP-201 clinical trial results

According to these results, 45% of patients treated with avutometinib in combination with defactinib saw their tumours shrink significantly.

Responses to the drug combination were particularly promising in those with a KRAS mutation, with 60% of patients experiencing significant tumour shrinkage. However, 29% of patients without the mutation also had an encouraging response.

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, which 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, treatment is over four times more effective than avutometinib alone.

RAMP-201 follows the Phase I FRAME trial, which tested avutometinib and defactinib in 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.

Results from FRAME indicate that this patient group lives an average of 23 months following treatment with this drug combination before their cancer progresses.

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: “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.”

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