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A new glimmer of hope is emerging for women with rare, treatment-resistant ovarian cancers. A new cocktail of drugs, tested in an advanced clinical trial, could offer an effective alternative to patients who had few therapeutic choices.
The results of this trial were recently presented by the Institute of Cancer Research (ICR) in the United Kingdom and are hailed by specialists as a significant advance. An update on this promising discovery, which could change the lives of many women.
Resistant forms of cancer that are difficult to treat
This phase II clinical trial, known as RAMP 201, focuses on a novel combination of two molecules: avutometinib and defactinib. The study is aimed at patients with recurrent low-grade serous ovarian cancer (who have experienced progression or recurrence of the disease after at least 1 line of treatment in a metastatic setting). When surgery does not provide a cure (in cases where the cancer has spread beyond the ovaries), 70% of people treated will see their cancer return after treatment.
This ovarian carcinoma preferentially affects young women and is not very sensitive to chemotherapy. One of the challenges is therefore to overcome this chemoresistance, in particular when the tumor presents a specific mutation of the KRAS gene, often resistant to traditional treatments.
Why does this combination work?
The results showed that among 115 participants, 31% saw their tumors shrink or stop growing after taking a combination of avutometinib and defactinib. A figure to be compared to the response rate to chemotherapy or hormonal therapy of 0 to 10% in patients with this rare ovarian cancer. And the results of patients with a KRAS gene mutation were even more promising: 44% of patients saw their tumor shrink.
The mechanism behind this effectiveness is based on the synergistic action of the two molecules. Avutometinib inhibits a molecular pathway called MAPK, which is frequently activated in KRAS-mutant cancers. For its part, defactinib blocks another signaling pathway, known as FAK, which allows cancer cells to reorganize and resist treatments. By combining these two actions, the researchers hoped not only to slow tumor growth but also to prevent the resistance mechanisms that make these cancers so difficult to treat.
Professor Susana Banerjee, lead author, said: “The combination of avutometinib and defactinib promises a new standard treatment for people with recurrent low-grade serous ovarian cancer. We are now looking to recruit patients for our phase 3 trial and hope that the results will continue to show better patient outcomes“.
Towards a change in care standards
The data from this trial will soon be submitted to the American authorities the Food and Drug Administration (FDA) for rapid marketing for patients suffering from this type of cancer with a KRAS mutation.
Clinicians hope this new drug combination will change practice globally for low-grade serous ovarian cancer and, importantly, improve outcomes for patients who today have little treatment options.