BRAF Mutations in Low-Grade Serous Ovarian Cancer and Response to BRAF Inhibition

• Published in: JCO precision oncology Vol. 2; p. 1
• Main Authors: Moujaber, Tania, Etemadmoghadam, Dariush, Kennedy, Catherine J, Chiew, Yoke-Eng, Balleine, Rosemary L, Saunders, Catherine, Wain, Gerard V, Gao, Bo, Hogg, Russell, Srirangan, Sivatharsny, Kan, Casina, Fereday, Sian, Traficante, Nadia, Patch, Ann-Marie, Pearson, John V, Waddell, Nicola, Grimmond, Sean M, Dobrovic, Alexander, Bowtell, David D L, Harnett, Paul R, deFazio, Anna
• Format: Journal Article
• Language: English
• Published: United States 01.11.2018
• ISSN: 2473-4284
• DOI: 10.1200/PO.17.00221

Low-grade serous ovarian carcinoma (LGSC) responds poorly to chemotherapy and is characterized by activating mutations in the Ras sarcoma-mitogen-activated protein kinase (RAS-MAPK) pathway, including oncogenic However, response to BRAF inhibitors is tumor-type specific. Significant improvement in survival is seen in patients with -mutant melanoma, but other cancer types, such as colorectal cancers, are generally less sensitive. We examined the frequency and characteristics of -mutated LGSC and described the response to treatment with BRAF inhibitors. Mutations were assessed in LGSC (N = 65) by using targeted, exome, and whole-genome sequencing. Patient characteristics, treatment, and clinical outcome were assessed, and the median follow-up time was more than 5 years. BRAF inhibitors were trialed in two patients with a somatic V600E mutation: one patient received dabrafenib monotherapy and was monitored clinically, biochemically (cancer antigen [CA]-125 levels), and with positron emission tomography (PET) imaging. Expression of the BRAF V600E protein in this patient was assessed by immunohistochemistry. Among patients with LGSC, nine (13.8%) of 65 had a somatic mutation. Of the nine patients with mutation-positive LGSC, four experienced progressive disease that did not respond to conventional chemotherapy. Two of the patients experienced progression quickly and died as a result of disease progression, and two received targeted treatment. Two patients with V600E mutation received BRAF inhibitors at relapse and both achieved durable responses. mutations are not uncommon in patients with LGSC and should be routinely tested, because BRAF inhibitors can be an effective treatment for these patients. The results highlight the need for targeted treatment in this rare tumor type, and a prospective study is needed to formally assess the response rate and clinical benefit.