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

5567 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 December 2023, 30 patients with a median age of 61 years (range:50-79), FIGO histopathological stage I (11.1%), Ⅱ(3.7%), III (59.3%) and IV (25.9%) were enrolled. Twenty-seven of these patients have been evaluated for efficacy. In the efficacy-evaluable population (n=12), the therapeutic evaluation showed that 7 and 13 patients achieved partial response and Stable disease respectively(with the standards of GCIC), yielding the ORR of 16.7% (7/27 95% CI: 11.8% to 46.6%). The DCR was 74.1% (20/27, 95% CI: 53.4% to 88.1%). The median PFS was 4.24 months (95% CI: 3.71m to 5.09m) and the median OS was 18.96 months (95% CI: 8.34m to 31.05m).With subgroup analyses, Patients who had received PARPi before and patients with baseline CA125 level >500 had significant prolongations in mOS and mPFS, respectively. The most common adverse events (AEs) were grade 1 or 2, which included laryngitis (44.4%), stomatitis (37.0%), hand-foot syndrome (29.6%), and fatigue (25.9%), diarrhea (22.2%), hypertension (14.8%),. The grade 3 AEs were hypertension (37.0%), hand-foot syndrome (3.7%), diarrhea (3.7%) and hyperuricemia (3.7%). No higher AEs or treatment-related death were observed. Conclusions: As a chemo-free regimens, anlotinib plus letrozole showed a promising efficacy with a favorable toxicity profile for patients with platinum-resistant recurrent ovarian cancer. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co. GYNECOLOGIC CANCER. Clinical trial information: NCT04720807 .