The U.S. Food and Drug Administration (FDA) has granted accelerated approval to a new oral drug combination for treating a rare form of ovarian cancer known as low-grade serous ovarian cancer (LGSOC). This approval offers a new treatment option for patients whose cancer tests positive for a specific gene change called the KRAS mutation. The treatment, known as Avmapki Fakzynja Co-Pack, combines two drugs avutometinib and defactinib and is designed for adult patients who have already undergone at least one prior treatment. The approval provides hope to approximately 6,000 to 8,000 women in the United States who are living with this difficult-to-treat condition.
LGSOC is a rare and slow-growing cancer, affecting an estimated 80,000 people worldwide, mostly women in their 20s-30s or 50s-60s. It accounts for about 5% of ovarian cancer cases, and approximately 30% of these cases involve mutations in the KRAS gene, which plays a significant role in the growth of the cancer. Unlike other types of ovarian cancer, LGSOC does not typically respond well to standard therapies and often recurs after treatment, making it challenging to manage. Despite the fact that many people with LGSOC can live for around 10 years, the disease can significantly impact physical health, fertility, and overall quality of life.
The FDA’s decision was based on the results of a clinical trial involving 57 patients with recurrent KRAS-positive LGSOC who had received at least one prior treatment. During the trial, patients were given oral doses of avutometinib twice a week and defactinib twice daily for the first three weeks of each four-week treatment cycle. They continued the treatment until the cancer progressed or severe side effects occurred. The results were promising: tumors shrank in 44% of the patients, with the response duration ranging from 3.3 months to 31.1 months.
The drug combination works by targeting two key proteins involved in cancer growth and treatment resistance. Avutometinib works by blocking MEK, a protein that promotes the growth of cancer cells. However, inhibiting MEK can lead to the activation of another protein, FAK, which can counteract the effects of the treatment. This is where defactinib comes in, as it blocks FAK, preventing the cancer from developing resistance to the treatment. Patients take Avmapki twice a week and Fakzynja twice a day for the first three weeks of each cycle, continuing as long as the treatment remains effective and the side effects are manageable.
While the drug combination offers significant benefits, it comes with a range of potential side effects. The most common include nausea, vomiting, diarrhea, abdominal pain, indigestion, constipation, mouth sores, itching, skin rashes, fatigue, joint and muscle pain, swelling, and changes in blood test results such as elevated liver enzymes and low blood cell counts. Some patients may also experience vision problems, shortness of breath, coughing, and urinary tract infections. Due to the potential for harm to a fetus, doctors advise women of childbearing age to use effective contraception during treatment. Patients will also undergo regular monitoring for liver function, skin toxicity, muscle disease (rhabdomyolysis), and vision problems during their therapy.
The approval of this new drug combination is a significant step forward in the treatment of LGSOC, providing a targeted option for patients who have few alternatives. However, the accelerated approval is contingent on further confirmatory trials to establish the long-term effectiveness and safety of the treatment. If the confirmatory trials yield positive results, the drug could receive full approval, offering lasting benefits to women suffering from this challenging cancer.
