Anlotinib (Al3818) Plus Pemetrexed In Patients With Recurrent Platinum-Resistant Advanced Epithelial Ovarian Cancer: A Single-Arm, Open-Label, Phase Ii Study.

e18078 Background: Anlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor that has previously shown clinical antitumor activity in various cancers, including the phase I study on tumors of female reproductive system. This phase II study (ChiCTR1800018192) aims to further evaluate the safety and efficacy of anlotinib combined with pemetrexed in patients with recurrent platinum-resistant advanced epithelial ovarian cancer. Methods: Patients who underwent cytoreductive operation, with histopathologically advanced epithelial ovarian cancer ( FIGO staging III or IV), and failed to previously platinum-based chemotherapies were considered eligible for enrollment to receive combined treatment of anlotinib (12 mg per day, days 1-14; 21 days per cycle) plus pemetrexed (0.5 g/m2, day 1; 21 days per cycle). Total duration of combined treatment contained 6 cycles, and subsequent maintenance treatment was anlotinib monotherapy (12 mg per day, days 1-14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint of this study was objective response rate (ORR) and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 July and 2019 October, 13 patients (female) with a median age of 55 years (range: 41 - 65), FIGO histopathological stage IIIA (7.7%) or IIIC (76.9%) or IV (15.4%) were enrolled. Over a mean follow-up period of 5.9 (95% CI: 3.4-8.3) months, therapeutic evaluation showed the incidence of partial response, stable disease, and progression disease was 38.5%, 53.8% and 7.7% respectively, yielding the ORR of 38.5% (5/13; 95% CI: 13.9%-68.4%) and the DCR of 92.3% (12/13; 95% CI: 64.0%-99.8%). The median PFS was not reached. Frequently occurring adverse events (AEs) were grade 1 or 2, including hand-foot syndrome (53.8%), allergic eruption (38.5%), mild hypertention (30.8%), fatigue (23.1%), diarrhea (23.1%), gum-pain (15.4%), and dry cough (15.4%). High grade AE was only observed in 1 patients with hemoglobin reduction of grade 4. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib (AL3818) plus pemetrexed showed a promising activity with an acceptable safety profile for previously platinum-treated patients with recurrent advanced epithelial ovarian cancer. Clinical trial information: ChiCTR1800018192.