Apatinib for patients with metastatic biliary tract carcinoma refractory to standard chemotherapy: results from an investigator-initiated, open-label, single-arm, exploratory phase II study

Abstract

Background: There is no standard therapy for metastatic biliary tract carcinoma (BTC) refractory to first-line chemotherapy. Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an activity against BTC xenografts in preclinical models. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with metastatic BTC. Methods: This is a single-arm phase II study [ClinicalTrials.gov identifier: NCT03427242]. Eligible patients were aged 18 years or older; histologically confirmed metastatic BTC; refractory or intolerance to at least one chemotherapeutic regimen; no prior use of anti-angiogenic targeted drugs; Eastern Cooperative Oncology Group performance status of 0–2. Patients received oral apatinib 500 mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progress free survival (PFS). The secondary endpoint was overall survival (OS), objective response rate (ORR) and treatment safety. Results: A total of 22 patients were recruited. All of them received apatinib medication. The median age was 63 (44–75) years old. Twenty patients received efficacy evaluation after treatment. The objective response rate (ORR) and disease control rate (DCR) were 15.0% and 60.0%, respectively. The median PFS was 2.73 months [95% confidence interval (CI): 1.74–3.72 months], with 6 months PFS rate of 27.3% (95% CI: 8.7–45.9%). The median OS was 4.81 months (95% CI: 3.16–10.9 months), with 12 months OS rate of 36.4% (95% CI: 16.2–56.6%). Nine out of 22 patients (40.9%) had grade 3/4 adverse events. The most common grade 3/4 adverse events were hand-foot skin syndrome [three (13.6%) patients] and hypertension [two (9.1%) patients]. No treatment-related death occurred. Conclusions: For patients with metastatic BTC, apatinib showed an anti-tumor activity with acceptable safety, which deserves the further clinical trial. This trial was prospectively registered on ClinicalTrials.gov [NCT03427242]. Date of first patient enrollment: 26 January 2018. Date of registration (date of first posted): 9 February 2018.

Effects of Gemcitabine and Oxaliplatin Combined with Apatinib on Immune Function and Levels of SIL-2R and sicAM-1 in Patients with Gallbladder Cancer

“…e literature [21] showed that gemcitabine, oxaliplatin, and apatinib significantly improved the shortand long-term outcomes and reduced the incidence of adverse effects in patients with biliary cancer. is finding is consistent with a previous study by [22] et al Improved treatment outcomes and increased overall survival time have been shown in patients with gallbladder cancer in a manner that is both very safe and within the tolerable range of possible side effects [23]. ere are certain limitations in this study, mainly including limited sample size, deviation of the study results from actual clinical data, which affects the reliability of the study report; insufficient time to assess the long-term effectiveness and resistance to treatment; and failure to consider the effects of drug treatment on other immune mechanisms.…”

“…The literature [ 21 ] showed that gemcitabine, oxaliplatin, and apatinib significantly improved the short- and long-term outcomes and reduced the incidence of adverse effects in patients with biliary cancer. This finding is consistent with a previous study by [ 22 ] et al Improved treatment outcomes and increased overall survival time have been shown in patients with gallbladder cancer in a manner that is both very safe and within the tolerable range of possible side effects [ 23 ].…”

Phase Ib study of anlotinib combined with TQB2450 in pretreated advanced biliary tract cancer and biomarker analysis

“… 11 In a systematic review of second‐line chemotherapies, which included 761 patients and 25 trials, mean PFS, OS, and ORR were merely 3.2 months, 7.2 months, and 7.7%, respectively. 28 Monotherapy with antiangiogenic TKIs, including regorafenib and apatinib, also yielded minimal efficacy in pretreated advanced BTCs, with median OS of 5.3 and 4.81 months, 29 , 30 respectively. As for ICI monotherapy, existing findings on second‐line use of programmed cell death protein 1 (PD‐1)/PD‐L1 inhibitors in BTCs are controversial, with a discrepancy in median OS ranging from 5.2 to 14.24 months.…”