Anlotinib combined with pemetrexed as a further treatment of patients with platinum-resistant ovarian cancer: A single-arm, open-label, phase II study

Abstract

<h3>Objectives:</h3> Anlotinib is a novel multi-target tyrosine kinase inhibitor for tumor angiogenesis and proliferative signaling. A previous retrospective study achieved the overall response rate (ORR) of 14.3% and the disease control rate (DCR) of 85.7% in platinum-resistant ovarian cancer (PROC) patients (pts) treated with anlotinib monotherapy, and the ORR of 33.3% and the DCR of 100% with anlotinib plus chemotherapy. The current prospective clinical trial (ChiCTR1800018192) aimed to further assess the efficacy and safety of anlotinib combined with pemetrexed and continued as maintenance therapy for PROC. <h3>Methods:</h3> Pts who had received at least two different chemotherapy regimens (including the first line platinum-based regimen), with histologically proven recurrent platinum-refractory or platinum-resistant epithelial ovarian cancer (including fallopian tube carcinoma and primary peritoneal carcinoma), ECOG 0-2, were considered eligible for enrollment to receive six 21-days cycles of anlotinib (12 mg QD from day 1 to 14) orally plus pemetrexed intravenously (0.5 g/m² on day 1). Anlotinib monotherapy was subsequently performed up to 1 year in patients without disease progression or intolerable toxicity. The primary endpoint was ORR, and the secondary endpoints included DCR, progression-free survival (PFS) and safety. <h3>Results:</h3> As of October 2020, 22 pts were enrolled. The median prior lines of chemotherapy was 4 (range, 2-10) and 55% of pts had ever received antiangiogenic therapy. A total of 17 pts had the confirmed best overall response assessments which inferred the ORR of 41.2% (PR in 7 pts; 95% CI, 18.4-67.1) and the DCR of 100% (PR in 7 pts and SD in 10 pts; 95% CI, 80.5-100). The median PFS was 9.3 months (95% CI, 6.0-12.6). Any grades of adverse events (AEs) were observed in 91% (20/22) of pts, containing frequent hand-foot syndrome (36%), hypertension (32%), allergic eruption (27%), fatigue (23%) and oral ulcer (14%). High grade AEs occurred in 3 pts, including 1 with grade III proteinuria, 1 with grade III ascites increase, and 1 with grade IV hemoglobin reduction. <h3>Conclusions:</h3> The treatment of anlotinib plus pemetrexed showed encouraging efficacy and satisfactory safety for platinum-resistant and -refractory, recurrent ovarian cancer pts who were previously treated with chemotherapy.