The purpose of this study is to evaluate the efficacy of addition of letrozole to the standard maintenance therapy in subjects following a primary diagnosis of Estrogen-receptor (ER) positive high and low grade epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) and subsequent primary treatment surgery and chemotherapy. Half of the participants will receive to the standard maintenance treatment, letrozole, whilst the other half receives placebo.

The study's primary hypothesis is that the treatment with letrozole increases progression free survival in comparison to the maintenance standard treatment (superiority trial).

Femara (letrozole) is an extensively investigated, marketed aromatase inhibitor (AI) widely used as treatment in the maintenance phase of estrogen-receptor (ER) positive breast cancer, as it inhibit the synthesis of estrogens. Estrogen is a well known driver of cancer growth in ER-positive tumors and a high percentage of the epithelial ovarian cancers express ER as well. Of which low grade ovarian cancers demonstrates the highest level of expression, supporting our strategy of a sub-group analysis (LOGOS). Therefore, letrozole in this study be investigated prospectively and evaluated as maintenance therapy after standard surgical and chemotherapy treatment in comparison to placebo (which is the current standard maintenance treatment) in subjects with primary, ER-positive low or high grade serous or endometrioid epithelial ovarian cancer (including fallopian tube and primary peritoneal cancer) of FIGO Stage II-IV, whose cancer has not progressed by the end of the platinum-based chemotherapy.

The objectives are to evaluate the letrozole maintenance treatment compared to placebo in terms of

• progression-free survival (PFS; primary endpoint)
• overall survival (OS)
• quality-adjusted progression free survival (QAPFS)
• time to first subsequent treatment (TFST)
• quality-adjusted time without symptoms of toxicity (Q-TWiST)
• health related quality of life (QoL) assessed by EQ-5D-5L, FACT-ES and FACT-O questionnaires

Methods: 540 for this study eligible subjects are 1:1 allocated in this randomized, controlled, double-blinded, multi-centre study to either the test (letrozole) or control (placebo) group. The maximum maintenance treatment duration is 5 years or until symptoms of toxicity or progression of underlying disease.

Health and health-related quality of life will continuously be assessed at study entry and during routine recalls which are scheduled every 12 weeks for the first 2 years, followed by every 24 weeks for the next 3 years. Procedures performed to assess the participants' health are the same as are performed during the regular routine ovarian cancer follow-up visits: blood tests, physical as well as gynaecological examinations and may include imaging. In addition, the participants are asked to complete during the study quality of life (QoL) specific questionnaires and wear an activity tracker for one week just before the scheduled visits. These assessments will be used for the evaluation of letrozole's efficacy and burden in comparison to the standard maintenance treatment. Survival follow-up data after the mainentance treatment duration of 5 years (study end) are obtained for up to another 7 years.

Inclusion Criteria:

• Patients must be ≥ 18 years of age
• Willing and able to attend the visits and to understand all study-related procedures.
• Primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low or high grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer
• (Interval-) debulking performed ECOG-Performance Status 0-2
• Signed informed consents (ICF-1; ICF-2)
• Paraffin-embedded tissue or paraffin-embedded cell block (from ascites) available
• Positivity (≥ 1%) for ER expression (only determined by Histopathology Core Facility of MATAO trial)
• At least 4 cycles of platinum-based chemotherapy (neoadjuvant allowed)
• Negative serum pregnancy test in women of childbearing potential who will get/have gotten a surgical resection or radiation sterilization, prior to the intervention in the therapeutical maintenance setting.

Exclusion Criteria:

• Progressive disease at the end of adjuvant treatment as defined in chapter 9.2.1 of protocol
• Women of childbearing potential (not having undergone a surgical or radiation sterilization and not getting a surgical resection, prior to the intervention in the therapeutical maintenance setting)
• Pregnant or lactating women
• Any other malignancy within the last 5 years which has impact on the prognosis of the patient
• < 4 cycles of chemotherapy in total
• Contraindications to endocrine therapy
• Inability or unwillingness to swallow tablets
• Patients with a known intolerance to galactose, lactase deficiency and glucose-galactose malabsorption