Everolimus and aromatase inhibitors for advanced and recurrent low-grade serous ovarian carcinoma.

Abstract

5569 Background: Treatment options for advanced and recurrent low grade serous ovarian carcinoma (LGSOC) are limited. Mutations in the PI3K/AKT/mTOR pathway have been described in LGSOC, but the use of everolimus and aromatase inhibitors (AI) has not been studied. Our primary objective was to determine the disease control rate (DCR) of everolimus (used off-label) and an AI in patients with LGSOC. Secondary objectives included progression free survival (PFS) and overall survival (OS). Methods: Diagnosis codes and medication lists were used to identify all patients with LGSOC from a single tertiary-care institution who were treated with everolimus and an AI between 2000- 2025. Data were extracted from the electronic medical record including demographics, staging, treatment, CA-125, imaging studies, reported side effects, recurrence, and survival data. Response was defined with RECIST 1.1 when measurable disease was present, otherwise clinical response was used. CA-125 was used independently as an additional measure of response. Results: A total of eight patients were identified, six with stage IIIC disease and two with stage IVB disease. Patients had between 0 and 4 debulking surgeries. Prior to treatment with everolimus and an AI, patients had 1-6 prior lines of therapy. All patients had received prior endocrine therapy, and five received chemotherapy. All patients were treated with everolimus 10mg and an AI (6 with letrozole and 2 with anastrozole). Patients remained on this regimen between 2 and 20 months (median = 15 months). One patient continues treatment today after 21 months of treatment. By RECIST criteria, two patients had a partial response, and four patients had stable disease. One patient has had clinically stable disease (soft tissue thickening and a stable CA-125) for 21 months and continues treatment. When comparing initial CA-125 to nadir while on treatment, CA-125 was stable in three patients and decreased 29%-64% (median = 50.5%) in four patients. One patient did not have CA-125 available in the EMR. Overall, the DCR was 87.5% (7 of 8 patients). Median PFS was 16.8 months, and median OS was 26 months. Of the seven patients who discontinued treatment, reasons for discontinuation included progression (n=3), death from disease (n=2), and inability to tolerate (n=2, one with grade 3 pneumonitis). Conclusions: In a group of eight patients with advanced LGSOC, everolimus and an AI demonstrated a DCR of 87.5%, a median PFS of 16.8 months, and a median OS of 26 months. While larger retrospective studies or prospective studies are needed, this regimen should be considered for advanced, recurrent LGSOC.