Letrozole for hormone receptor-positive low-grade ovarian cancer: Preliminary toxicity results of a phase III trial

Background: Epidemiological and retrospective studies suggest that letrozole may improve outcomes in low-grade serous carcinoma of the ovary (LGSCO) by targeting estrogen-driven tumor progression. Methods: We designed a multicenter, randomized, open-label, phase III trial to compare letrozole versus standard chemotherapy (carboplatin plus paclitaxel) in prolonging progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), quality of life (MENQoL), and musculoskeletal pain (BPI-SF). Translational objectives explore mutational and expression profiles (NGS, RAD51/BRCA1 foci) and circulating tumor DNA (ctDNA) as markers of treatment response. Eligible patients are postmenopausal women with stage III–IV ER/PgR-positive LGSCO after primary cytoreductive surgery. Patients are randomized 1:1 to letrozole 2.5 mg daily until progression or unacceptable toxicity, or to carboplatin-paclitaxel for 6–8 cycles. Disease progression is assessed by RECIST, CA-125, and imaging every 3–6 months. Results: As of March 2025, 46 patients have been randomized (23 per arm). Preliminary analysis shows a favorable safety profile for letrozole compared with chemotherapy. Conclusions: Early findings suggest letrozole is well tolerated and may represent a viable therapeutic option for hormone receptor-positive LGSCO. Ongoing molecular and clinical analyses will clarify its role in this rare subtype. Trial registration: ClinicalTrials.gov Identifier: NCT05601700; https://clinicaltrials.gov/study/NCT05601700