Primary objective:~To determine if letrozole is superior to standard chemotherapy in terms of progression-free survival (PFS) in patients with advanced low-grade serous epithelial ovarian carcinoma positive for estrogen and/or progesterone receptors.~Secondary objectives:~to evaluate the response of tumor to letrozole compared with standard chemotherapy in terms of objective response rate (ORR);~to test the predictive effect of ER and PgR on response to letrozole in terms of PFS and ORR;~to evaluate the possible negative association between the effect of letrozole, in terms of PFS and ORR, and the proliferative index Ki67;~to evaluate the impact of letrozole compared with the impact of standard chemotherapy on patients' health related quality of life evaluated by Menopausal Quality of Life Questionnaire (MENQOL);~to evaluate the impact of letrozole compared with standard chemotherapy on patients' musculoskeletal pain evaluated by Brief Pain Inventory - Short Form (BPISF);~to evaluate the effect on overall survival (OS). As most patients will recur and will be switched to chemotherapy and vice versa, OS is not expected to be significantly different;~to evaluate the safety of letrozole compared with standard chemotherapy according to CTCAE v 5.0.~Translational objectives:~to characterize the mutational profile and gene expression of the disease by NGS (next-generation sequencing) methodology on tissue samples;~to evaluate the circulating tumor DNA (ctDNA) on liquid biopsies as a tool to monitor the disease response.
This is an Italian, multicenter, randomized, open-label phase III trial which will evaluate if Letrozole is superior to standard adjuvant chemotherapy in patients with hormone receptor positive low-grade serous epithelial carcinoma of the ovary (LGSCO).~The hypothesis is that letrozole will significantly prolong median progression free survival (PFS) compared with the standard chemotherapy treatment, namely carboplatin AUC 5 and paclitaxel 175 mg/m2.