Anlotinib plus letrozole in patients with platinum-resistant recurrent ovarian cancer: A prospective, single-arm, open-label, phase II study.

Abstract

e17545 Background: Studies have suggested that estrogen regulates the malignant transformation of ovarian surface epithelial cells, stimulates the growth and migration of cancer cells. and promotes the VEGF expression in epithelial ovarian cancer. Anlotinib is a novel multi-target tyrosine kinase inhibitor, inhibiting tumor angiogenesis and proliferative signaling. In this study, we evaluate the activity of anlotinib combined with letrozole in patients with estrogen receptor positive, platinum-resistant recurrent ovarian carcinoma (NCT04720807). Methods: Patients who have previously received two or more chemotherapy treatments, with histopathologically confirmed high-grade serous ovarian cancer (including salpingo carcinoma and peritoneal carcinoma), estrogen receptor (ER) positive and ECOG 0-2 were considered eligible for enrollment. Anlotinib was taken orally (10mg mg qd, d1-14, 21 days per cycle), and letrozole was taken orally (2.5mg qd, d1-21, 21 days per cycle). The treatment was continued until disease progression, death, or intolerant toxicity. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), duration of remission (DOR) progression free survival (PFS), overall survival (OS) and safety. Results: Between September 2020 and November 2021, 13 patients with a median age of 62 years (range:53-72), FIGO histopathological stage IC (23.1%), IIIC (53.8%) and IV (23.1%) were enrolled. Twelve of these patients have been evaluated for efficacy. In the efficacy-evaluable population (n=12), the therapeutic evaluation showed that 2 and 7 patients achieved partial response and Stable disease respectively, yielding the ORR of 16.7% (2/12, 95% CI: 3.3 to 54.3). The DCR was 75% (9/12, 95% CI: 39.3 to 93.3). The median PFS was 6.25 months (95% CI: 2.3m to not reached) and the median OS was not reached. The most common adverse events (AEs) were grade 1 or 2, which included laryngitis (69.2%), hypertension (53.8%), stomatitis (38.5%), diarrhea (30.8%), hand-foot syndrome (23.1%), and hyperuricemia (23.1%). The grade 3 AEs were hypertension (38.5%), diarrhea (7.7%) and hyperuricemia (7.7%). No higher AEs or treatment-related death were observed. Conclusions: Conclusions Anlotinib plus letrozole showed a promising efficacy with a favorable toxicity profile for patients with platinum-resistant recurrent ovarian cancer. The trial is ongoing and more data will be provided in the future. Clinical trial information: NCT04720807.