LAUSR

Objectives: Anlotinib is an oral multi-kinase inhibitor that widely inhibits VEGFR, PDGFR, FGFR and c-kit. Previous researches have shown clinical antitumor activity of anlotinib in various cancers, including the gynecologic tumors. This investigator-initiated, single-arm, open-label, phase II trial assessed the efficacy and safety of anlotinib combined with chemotherapy (platinum and paclitaxel) and continued as maintenance therapy for the primary treatment of ovarian cancer. Methods: Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage I to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. All enrolled patients were treated with six 21-day cycles of chemotherapy intravenously (platinum and paclitaxel, regimens were chosen by the investigators according to the guidelines) and anlotinib orally (12 mg qd, d1-14; 21 days per cycle) till disease progression, death or intolerant toxicity. Therapeutic effects are evaluated every 6 weeks. The primary endpoint was objective response rate (ORR) and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Results: Between August 2018 and April 2020, 17 patients (female) with FIGO histopathological stage IC (11.8%), II(5.9%), IIIC (35.3%) and IV (41.2%) were enrolled with a median age of 56 years (range: 37-82). Therapeutic evaluation showed the incidence of complete response, partial response, stable disease and progression disease was 0%, 58.8%, 23.5% and 17.6% respectively, yielding the ORR of 58.8% (10/17; 95% CI:32.9-81.6) and the DCR of 82.4% (14/17; 95% CI:56.6-96.2). Further, the ORR of ovarian cancer with or without metastatic lesions was 50% (6/12; 95% CI:21.1-78.9) and 80% (4/5; 95% CI: 28.4%-99.5%) respectively. The median PFS was 11.8 months (95% CI: 4.5-19.1). Most of the occurring AEs were grade 1-2 and >10% Grade 1 AEs included hypertension (58.8%), oral mucosa ulcer (35.2%), hand-foot syndrome (35.2%) and thrombocytopenia (17.6). Only two hypertension (11.8%) and three oral mucosa ulcer (17.6%) were grade 3. No high grade AEs were observed in these 17 patients. Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Anlotinib plus chemotherapy showed a promising efficacy with a favourable toxicity profile in the first-line treatment for advanced ovarian carcinoma patients, and maybe better in the patients without metastasis which needs further verification.