A phase II study of anlotinib with cediranib as a second-line treatment for patients with advanced biliary tract cancers (aBTCs).

Abstract

e16712

Background: Gemcitabine combined with cisplatin (GP) is currently used as a standard first-line chemotherapy regimen for aBTCs, However, the median overall survival (mOS) is only about 11.7 months, and there is no standard treatment option for patients who failed GP therapy. In this study, we aimed to investigate the efficacy and safety of anlotinib with cediranib as a second-line treatment for patients with aBTCs. Methods: A monocenter single-arm phase II study was conducted at the First Affiliated Hospital of Zhengzhou University. Patients with measurable aBTCs and progressed on GP were enrolled in this study. Patients received cediranib 200mg, on day1 + anlotinib 12mg on day1-14, Q3W until disease progression, intolerance of toxicity, investigator/patient decision to withdraw or other reasons specified in the protocol. Response (RECIST1.1) was assessed every 8 weeks. Plasma, stool and tumor tissues were collected for exploratory analyses. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and drug safety. Results: We planned to include 20 patients. So far 9 patients were enrolled in this study, 66.7% (6/9) were men, 33.3% were women. The median age was 56y (43y-61y). The primary sites of the tumor were intrahepatic biliary (66.7%, 6/9) and gallbladder (33.3%, 3/9). At data cutoff (Dec 14, 2019), the median duration of follow-up was 2.5mos (range, 1.2 to 4) and all of the patients were still under treatment. 8 patients have undergone at least one efficacy evaluation, of which 2 (25%) PR, 5 SD (62.5%), DCR was 87.5% ((7/8). An SD patient had a long-term intermittent fever, which considered to be tumor fever, the body temperature returned to normal after 1 cycle of treatment. 1 patient was considered to be undefined because, at the first evaluation, the liver lesions were reduced however the lymph nodes in the retroperitoneum were enlarged. The median PFS and OS not yet reached. Grade 3-4 treatment-related adverse events (TRAEs) occurred in 11.1% (1/9) of patients. TRAEs led to discontinuation in 1 patient (grade 3 hypertension). TRAEs led to dose reduction of anlotinib in 2 patients. No TRAEs were fatal. Conclusions: The primary result showed that the combination of anlotinib and cediranib was well tolerated and demonstrates encouraging efficacy than historical control in second-line treatment for aBTC. Updated data, including safety, efficacy, and biomarkers will be presented. Clinical trial information: ChiCTR1900022003 .