Letrozole for Estrogen/Progesterone Receptor Positive Low-grade Serous Epithelial Ovarian Cancer (LEPRE Trial)

Inclusion Criteria: I - 1. Age ≥ 18 years. I - 2. Newly diagnosed, low-grade serous carcinoma of the ovary including cancer of fallopian tube and peritoneum (invasive micropapillary serous carcinoma or invasive grade 1 serous carcinoma). This is to be confirmed via nuclear p53 immunohistochemistry testing by a central pathology review performed at the Coordinating Centre. I - 3. Immunohistochemically determined positivity (≥ 10%) for ER and/or PgR expression. This is to be confirmed by centralized review. I - 4. Patients must have undergone an upfront surgery with maximal cytoreductive effort, with either optimal or suboptimal residual disease status. I - 5. Stage III-IV according to 2018 FIGO classification. For proper staging: * Patients must have undergone contrast-enhanced CT-scan of the chest, abdomen and pelvis within 28 days prior to randomization. If CT-scan is not recommended (e.g. for allergy to contrast agent) MRI or 18F-FDG PET/CT-scan are allowed. * The imaging evaluation must be accompanied by an anamnestic and physical examination within 14 days prior to randomization. I - 6. Postmenopausal, defined as any of the following criteria: * Patients who underwent bilateral salpingo-oophorectomy; * Monolateral salpingo-oophorectomy, amenorrhea for 12 or more consecutive months and age ≥60 years; * Monolateral salpingo-oophorectomy, amenorrhea for 12 or more consecutive months, age \<60 years and FSH and serum estradiol levels within the laboratory's reference ranges for post-menopausal women. I - 7. Randomization must take place within 60 days of primary cytoreductive surgery. I - 8. Eastern Cooperative Oncology Group - performance status (ECOG-PS) 0-1. I - 9. To be able to take oral medications. I - 10. Adequate bone marrow, hepatic and renal functions as defined below: * Absolute neutrophil count (ANC) ≥ 1500/mm3 * Platelets ≥ 100,000/mm3 * Hemoglobin ≥ 10.0 g/dL * Total bilirubin ≤ 1.5 x Upper Limit of Normal (ULN) * ALT and AST ≤ 3.0 x ULN * Alkaline phosphatase ≤ 2.5 x ULN * Albumin ≥ 2.8 g/dL * Serum creatinine ≤ 1.5 x ULN. I - 11. Written informed consent obtained prior to any study-specific procedure. Exclusion Criteria: E - 1. Other malignancy within the last 5 years, except for non-melanoma skin cancer adequately treated. E - 2. Neoadjuvant chemotherapy or radiotherapy for the treatment of this disease. E - 3. Previous hormonal therapy for the treatment of this disease. E - 4. Known hypersensitivity to letrozole or known hypersensitivity/intolerance to carboplatin/paclitaxel therapy. E - 5. Active or uncontrolled systemic infection. E - 6. Known central nervous system metastases. E - 7. Severe cardiac disease, such as myocardial infarction or unstable angina within 6 months prior to randomization. E - 8. New York Heart Association (NYHA) Class III or greater congestive heart failure. E - 9. Neuropathy grade 2 or higher. E - 10. History of fractures of the spine or femur not properly treated. E - 11. Known osteoporosis (dual-energy x-ray absorptiometry (DEXA) of the femoral neck T score of -2.5 or lower) not adequately treated with bisphosphonates or RANKL inhibitors. E - 12. Concomitant use of inducers of CYP3A4 (e.g. phenytoin, rifampicin, carbamazepine, phenobarbital, and St. John's Wort) which may reduce exposure to letrozole. Concomitant use of medicinal products with a narrow therapeutic index that are substrates for CYP2C19 (e.g. phenytoin, clopidrogel) that may have their systemic serum concentrations altered by letrozole. E - 13. Concurrent severe medical problems or any condition that would significantly limit full compliance with the study.