Impact of Hormonal Status on Outcome of Aromatase Inhibitor Maintenance Post-adjuvant Chemotherapy in High Grade Serous Ovarian Cancer (HGSOC): A Phase II Study

Abstract

Background: Epithelial ovarian cancer (EOC) is a hormone-related malignancy where receptor status serves as a prognostic factor. While the role of molecular targets, including estrogen receptor (ER) and progesterone receptor (PgR), in predicting tumor response is debated, studies suggest hormonal therapy may benefit advanced EOC patients. However, its efficacy based on tumor characteristics and specific agents remains unclear. We hypothesized that endocrine therapy could serve as maintenance treatment for ER/PgR-positive FIGO stage III/IV high-grade serous ovarian cancer (HGSOC) after debulking surgery and adjuvant chemotherapy. Methods: This prospective, phase II randomized clinical study evaluated the safety and efficacy of maintenance endocrine therapy using aromatase inhibitors (AIs), letrozole (2.5 mg daily) administered off-label. Patients received treatment for up to five years or until experiencing adverse effects, symptomatic recurrence, or requiring further chemotherapy. Correlations with ER and PgR immunohistochemistry were assessed. Results: A total of 84 HGSOC patients underwent debulking surgery (53 with prior neoadjuvant chemotherapy) followed by adjuvant platinum-based chemotherapy. Participants were randomized (2:1) to either AI maintenance (n=56, 66.7%) or observation. Median treatment duration was 13 months (range: 2–26), with no adverse events necessitating discontinuation. While no significant differences were observed in relapse rates or disease-free survival overall, younger patients (<50 years) showed a trend toward worse outcomes, warranting further investigation. Conclusions: Maintenance endocrine therapy after debulking surgery and chemotherapy in HGSOC, regardless of receptor status, does not provide significant benefit. However, its low cost and manageable toxicity profile highlight its potential as a therapeutic option in select cases. These findings emphasize the need for further studies to identify subgroups that may benefit and refine predictive biomarkers for improved clinical outcomes.