According to a recent article, trametinib has proven to be successful in treating a rare ovarian cancer subtype, which is a major advancement in treating those with this rare ovarian and peritoneal cancer subtype.

Ovarian Cancer

Ovarian cancer is a type of cancer that forms in an ovary. An ovary is one of two almond-shaped organs found on each side of the uterus that store eggs and produces the hormones estrogen and progesterone. Depending on the type and stage, malignant cells are found inside, near, or on the outer layer of the ovaries. Common areas where the cancer may spread from the ovary include the abdomen lining, bowel and bladder lining, lymph nodes, lungs, and liver. There are four types of ovarian cancers:

1. Epithelial tumors, which refer to the thin layer of tissue that covers the ovaries and account for 90% of ovarian cancer cases
2. Germ cell carcinoma tumors, in which the cancer begins in the cells that form the eggs and account for 5% of ovarian cancer diagnoses
3. Stromal carcinoma tumors, in which the cancer develops in the connective tissue cells that hold the ovary together and produce estrogen and progesterone and account for 5% of ovarian cancer diagnoses
4. Small cell carcinoma of the ovary (SCCO), which is a rare, highly malignant tumor that accounts for 0.1% of ovarian cancer diagnoses

The staging of ovarian cancers is the following:

• Stage I: Cancer is found in one or both ovaries
• Stage II: Cancer has spread to the pelvis
• Stage III: Cancer has spread to the abdomen
• Stage IV: Cancer has spread to other parts of the body

Symptoms:

The frequency and/or number of symptoms are key factors in the diagnosis of ovarian cancer, and symptoms become more noticeable as the cancer progresses. Common symptoms include:

• Bloating
• Pelvic pain
• Abdominal swelling
• Loss of appetite
• Urinary symptoms (urgency or frequency)

Symptoms of a cancer within the stromal carcinoma group include:

• Abnormal uterine bleeding
• Endometrial hyperplasia (thickening of the uterus that causes bleeding)
• Breast tenderness
• Vaginal secretions
• Virilizing symptoms due to increased testosterone
• Increased abdominal girth
• Enlarging abdominal mass
• Irregularities in the menstrual cycle

Trametinib

Trametinib is an MEK inhibitor used to reduce the risk of disease progression or death in patients with low-grade serous ovarian carcinoma. 

The Study

David Gershenson, MD, professor of gynecologic oncology and reproductive medicine, led the study at the University of Texas MD Anderson Cancer Center. The goal of the study was to use trametinib to find progression-free survival (PFS) and the overall response rate (ORR).

The study went on from February of 2014 until April of 2018. It was a randomized, open-label (both the patient and the researchers know which treatment is given), multi-center, phase 2/3 trial. A total of 260 patients participated and were randomized to either receive trametinib or standard of care treatment (SOC).

The patients who were chosen to receive trametinib were given 2mg of the drug once every day. For the patients who were a part of the SOC group, they had 1 or 5 SOC treatments. The SOC treatments included the use of intravenous paclitaxel, intravenous pegylated liposomal doxorubicin, intravenous topotecan, oral letrozole, or oral tamoxifen.

The primary endpoint of the trial was determined to be PFS, with secondary endpoints of safety, ORR, quality of life, and overall survival (OS).

Results

Of the patients who received trametinib, 78% had progression-free survival (PFS) events. For patients who received the standard of care (SOC), 89% had PFS events. The median PFS for patients was 13 months in patients who received trametinib and 7.2 months in patients who received SOC. Finally, the overall response rate (ORR) was 26% in patients who received trametinib and only 6% for patients who received SOC. Furthermore, 59% of the patients who were treated with trametinib had stable disease for at least 8 weeks. 

The median duration of response for the trametinib group was 13.6 months compared to 5.9 months in the SOC group. Out of the 260 patients who participated in the trial, 111 (43%) died. 51 of the patients who died were a part of the trametinib group and the other 60 patients were a part of the SOC group. The median overall survival (OS) of the trametinib group was 37.6 months, and in the SOC group it proved to be 29.2 months.

The most common adverse events (AEs) that were associated with the trametinib group were skin rash, anemia, hypertension, diarrhea, nausea, and fatigue. For the SOC group, abdominal pain, nausea, anemia, and vomiting were the most common AEs. There were no deaths in either groups that were a result of the treatment.

The results of this study are a major advancement in treating patients who are diagnosed with a rare ovarian cancer subtype. The next steps are to use this success to create more drugs or regimens to treat this disease.