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

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.