A Phase II, Single-Arm, Prospective Clinical Trial for the Efficacy and Safety of Apatinib Combined With Capecitabine in Therapy for Recurrent/Metastatic and Persistent Cervical Cancer After Radiochemotherapy

Abstract

Cervical cancer is mainly treated by surgery, radiotherapy and chemotherapy. However, there are also some patients with treatment failure, such as residual tumors, recurrence or metastasis within a short period of time after the initial treatment. Apatinib is a targeted drug for a small molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor. We aimed to assess the efficacy and safety of apatinib combined with capecitabine in patients with recurrent/metastatic and persistent cervical cancer after radiochemotherapy.In this phase Ⅱ, single-arm, prospective study done in Guizhou province in China, eligible patients were aged 18-70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of radiochemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable lesions. Patients received capecitabine 2000mg/m2 divided into morning and evening every day and apatinib 250mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1 and Progression-free survival (PFS). Disease control rate (DCR), overall survival (OS),1-year survival rate and safety were the second endpoints.Between August 2018 and May 2020, 28 patients were enrolled and received study treatment. The median age was 52(range, 34-67) years. The median previous treatment lines were 2 (range, 2-5). As of Jan 1, 2021, median follow-up was 10.18 months (range, 3.4-29). 12 (42.9%; 95%: CI 23.5-62.3) of 28 patients who had at least one post-baseline tumor assessment (efficacy evaluation population) achieved an objective response, including 3 (10.7%) complete response (CR), and 9 (32.1%) partial response (PR). The median duration of response was 1.57months(range,0.9-2.17). The DCR was 82.1% (95% CI: 67.3% -97.2%). Median progression-free survival (PFS) was 4.7 months (95% CI: 1.2-18.6). The one-year survival rate was 54.8%, and the longest administration time was 18.2 months.10 (35.7%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (7.1%), emesis (7.1%), myelosuppression (7.1%). Notably, one patient discontinued maintenance therapy after 13 months because of coronary artery stenosis which is a rare toxic side effect of apatinib.Apatinib combined with capecitabine showed promising antitumor activity and tolerable toxicities in patients with recurrent/metastatic and persistent cervical cancer after chemotherapy.