Selumetinib Controlled Recurrent Low-Grade Serous Ovarian Cancer

Selumetinib, a small-molecule MEK inhibitor, demonstrated the ability to control low-grade serous ovarian or peritoneal cancer, according to phase II study results presented at the AACR Annual Meeting 2012, held here March 31 - April 4.

The first line of defense against low-grade serous ovarian cancer is surgery, followed by cytotoxic chemotherapy. However, this is a slow-growing cancer and does not respond well to traditional chemotherapies, which target fast-growing cells.

Seeking a more rational treatment approach, Gynecologic Oncology Group (GOG) researchers led by John Farley, M.D., a professor at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center in Omaha, Neb., used selumetinib to target the MEK-1/2 protein kinase in the MAPK pathway, which is known to mutate in this form of cancer.

GOG researchers assigned 52 women to 100-mg doses of selumetinib orally twice daily in four-week cycles; 33 percent underwent 12 or more cycles. Prior to the study, 58 percent of patients had received three or more rounds of chemotherapy.

Selumetinib controlled the disease in 81 percent of patients. Specifically, eight patients had complete or partial responses to treatment, and 34 had stable disease. The median survival rate without cancer progression was 11 months, and 63 percent of patients had progression-free survival longer than six months. In addition, selumetinib was well tolerated, with three patients experiencing grade 4 adverse events.

“The results were striking,” said Farley. “Many of the patients in the study had received multiple rounds of chemotherapy and were running out of options. By using these tumors’ historical inherent molecular aberrations to select patients for a treatment that in theory could exploit these abnormalities, we took an important step toward individualized cancer therapies.”

How common is ovarian cancer?

A woman’s risk of getting ovarian cancer during her lifetime is about one in 67. The risk of getting this cancer and dying from it is one in 95. Ovarian cancer is the eighth most common cancer in women, excluding skin cancer. It is the fifth leading cause of cancer death in women.

What are the symptoms of ovarian cancer?

The initial symptoms are similar to gastrointestinal illness and indigestion, making the disease hard to diagnose. For this reason, many women are not diagnosed until late in the development of ovarian cancer. Signs and symptoms of ovarian cancer may include:

- general abdominal discomfort and/or pain (gas, indigestion, pressure, bloating, cramps)
- nausea, diarrhea, constipation and frequent urination
- loss of appetite
- feeling of fullness even after a light meal
- weight gain or loss with no known reason
- abnormal bleeding from the vagina may occur as a late symptom

These symptoms may be caused by ovarian cancer or by other less serious conditions. It is important to check with a doctor about any of these symptoms.

In addition to studying the impact of selumetinib on this type of ovarian cancer, investigators were also interested in how patients with RAS/RAF mutations responded to the drug. The team analyzed the tumor DNA from 34 patients, 62 percent of whom had some form of RAS/RAF mutation. Ultimately, they found that RAS/RAF mutations had no impact on patient response.

The study was funded by the National Cancer Institute.

About the AACR
Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policy makers about the value of cancer research and related biomedical science in saving lives from cancer.


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