New therapeutic opportunities for low-grade serous ovarian cancer. Issue 5 (October 2021) - Moujaber, Tania
Abstract : Low-grade serous ovarian cancer (LGSC) is a morphologically and molecularly distinct subtype of ovarian cancer, accounting for ~10% of serous carcinomas. Women typically present at a younger age and have a protracted clinical course compared with the more common, high-grade serous ovarian cancer. Currently, primary treatment of LGSC is the same as other epithelial ovarian cancer subtypes, with treatment for most patients comprised of debulking surgery and platinum/taxane chemotherapy. Primary surgical cytoreduction to no visible residual disease remains a key prognostic factor, however the use of platinum-based chemotherapy in both the upfront and relapsed setting, is being questioned due to low response rates in LGSC. Most LGSC express steroid hormone receptors and selected patients may benefit from endocrine maintenance therapy following chemotherapy, in particular those with evidence of residual disease at completion of surgery. In the recurrent setting, while hormonal therapies may offer disease stabilization with relatively low toxicity, objective response rates remain low. Strategies to increase response rates, including combining with CDK4/6 inhibitors, are being investigated. LGSC have a high prevalence of activating somatic mutations in mitogen-activated protein kinase pathway genes, most commonly in KRAS, BRAF and NRAS. Trametinib, a MEK inhibitor, has shown efficacy over chemotherapy and endocrine therapy. The use of combination targeted therapies, immunotherapy and anti-angiogenic agents, remain active areas of investigation for the treatment of LGSC.