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Selumetinib benefited patients with recurrent low-grade ovarian cancer
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Selumetinib was found to exhibit high response rates in the treatment of recurrent low-grade serous carcinoma of the ovary or peritoneum, according to results of an open-label, single-arm phase 2 study.
The drug also was well tolerated, researchers said.
Patients with low-grade serous ovarian carcinomas typically are diagnosed at a younger age and experience a longer OS than patients with high-grade serous carcinoma. However, low-grade serous carcinoma has exhibited chemoresistance, both to first-line agents and in the recurrent disease setting.
Previous studies have found that both serous ovarian tumors of low malignant potential and low-grade serous carcinomas of the ovary demonstrate a higher frequency of KRAS and BRAF mutations, a higher frequency of expression of active MAPK and a lower frequency of TP53 mutations than high-grade serous carcinomas.
David M. Gershenson
To determine whether these mutations in the MAPK pathway could be targeted to control tumor growth, David M. Gershenson, MD, professor in the department of gynecologic oncology at The University of Texas MD Anderson Cancer Center, and colleagues enrolled 52 women (aged at least 18 years) with recurrent low-grade serous ovarian or peritoneal carcinoma.
Patients received selumetinib (AstraZeneca) 50 mg orally twice daily until progression of their disease.
Eight patients (15%) demonstrated an objective response to treatment, results showed. One patient had a complete response and seven had partial responses. Thirty-four patients (65%) patients exhibited stable disease.
Treatment-related grade 3 or 4 toxicities included gastrointestinal, dermatological, metabolic, fatigue, anemia, pain, constitutional and cardiac events.
“In the current study, selumetinib has substantial activity in recurrent low-grade serous tumors, particularly when compared with that achieved with cytotoxic chemotherapy for recurrent low-grade serous tumors,” Gershenson and colleagues wrote. “The regimen is also associated with less toxicity than are cytotoxic regimens. The results of this study suggest inhibitors of the MAPK pathway should be further investigated in patients with [low-grade serous tumors].”
Disclosure: Gershenson received funding from the NCI and the Gynecologic Oncology Group.
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