SC, LY and YC wrote the original manuscript

SC, LY and YC wrote the original manuscript. (CisGem) chemotherapy. Methods Patients with advanced BTCs who progressed after CisGem were recruited. A combination regimen of lenvatinib (8/12 mg daily) plus PD-1 antibody (200/240 mg injection every 3 weeks) was prescribed. Clinicopathological information and therapeutic Calcifediol monohydrate outcome, including tumor subtypes, biomarkers, treatment duration, adverse events (AE), progression-free survival (PFS), and overall survival (OS), were recorded and estimated. Results A total of 351 patients with BTCs were reviewed and 74 were recruited eventually: 35 had intrahepatic cholangiocarcinoma (47.3%), 4 had extrahepatic cholangiocarcinoma (5.4%), and 35 had gallbladder cancer (47.3%). The median administered cycles of PD-1 antibody were 6.43 (95% CI: 5.83C7.04) cycles, and the median duration of lenvatinib medication was 21.0 weeks (95% CI: 18.04C23.93). Twenty-eight patients (37.83%) experienced detectable objective response per RECIST1.1 within a median follow-up duration of 15.0 months. The objective response rate (ORR) was 20.27% (95% CI: 10.89%C29.65%), and the disease control rate (DCR) was 71.62% (95% CI: 61.11%C82.14%). The median PFS and OS were 4.0 months (95% CI: 3.5C5.0) and 9.50 months (95% CI: 9.0C11.0), respectively. Seventy-three patients (98.64%) reported AEs and 39 (52.70%) experienced grade 3 AEs. In subgroup analyses, tumoral PD-L1 expression 50% and tumor mutation burden (TMB) 2.5 Muts/Mb were associated with prolonged PFS. Conclusion Lenvatinib plus PD-1 antibody treatment shows an active trend towards improving survival in patients with advanced BTCs after failure with Calcifediol monohydrate CisGem chemotherapy. The treatment-related AEs are Calcifediol monohydrate worthy of attention and are manageable. Keywords: lenvatinib, PD-1 inhibitor, immunotherapy, target therapy, biliary tract cancer, second-line agents Introduction The incidence of biliary tract cancer (BTC), formerly considered rare, increased significantly in the last two decades globally (1). Although increasing types Rabbit polyclonal to PDE3A of biological agents and immune-oncology regimens emerged in hepatocellular carcinoma, there are limited therapies available in advanced BTC. Cisplatin/gemcitabine (CisGem)-based chemotherapy is currently recommended as the standard first-line therapy in advanced BTCs, although both its efficacy and tolerance are suboptimal (2). In the recent ABC-06 study, FOLFOX (folinic acid, fluoroutacil, and oxaliplatin) was evaluated as a second-line treatment after progression with CisGem (3). It demonstrated only a modest 1-month survival benefit against best supportive care. This frustrating result prompts novel effective therapeutic strategies to be tested so as to qualify as a second- or above-line therapy. Although immunotherapy has revolutionized the treatment standard of several hematological and solid malignancies, its role in advanced BTC is still unclear. Monotherapy with immune checkpoint inhibitors Calcifediol monohydrate (ICIs) in advanced BTC has presented conflicting results, suggesting further investigation in agent combination and deeper insight into subgroup selection. Lenvatinib is an inhibitor of receptor tyrosine kinases, targeting vascular endothelial growth factor receptors (VEGFR1C3), fibroblast growth factor receptors (FGFR1C4), KIT, and RET (4). Owing to its capability of inhibiting multiple kinases in nanomole concentration, lenvatinib is now broadly used in the treatment of a variety of solid cancers, including differentiated thyroid cancer, hepatocellular carcinoma, and renal cell carcinoma, as a single agent or in combination with another drug (5). Several preliminary assessments of lenvatinib monotherapy or combination therapy with ICIs as first- or non-first-line therapy were reported, but the results were suboptimal and need further validation (6C9). Hereby, we reported a single arm of patients with refractory advanced BTCs, treated with lenvatinib plus programmed cell death protein-1 (PD-1) antibody as a second- or above-line systemic therapy. Materials and methods Study Design and Patients This was a single-center retrospective study assessing the efficacy and safety of TKI lenvatinib associated with PD-1 antibody Calcifediol monohydrate as a systemic therapy beyond 1st-line after the failure of CisGem chemotherapy at a hepatobiliary specific referral center (Eastern Hepatobiliary Surgery Hospital). BTC patients who received lenvatinib plus PD-1 antibody synchronously or successively as a second- or above-line systemic therapy from January 1, 2019 to March 31, 2021 were reviewed. This study was approved by the Institutional Ethics Committee of Shanghai Eastern Hepatobiliary Surgery Hospital. The study protocol conformed to the principles of the Declaration of Helsinki. The statistical analysis was conducted according to the intention-to-treat principle. All the data were updated and censored on February 28, 2022. The patients with advanced BTCs who experienced progression after CisGem in first-line therapy were permitted to enroll. Advanced BTC was defined as initially diagnosed unresectable BTC (pathologically proved by biopsy or surgical specimen, multiple lesions, extrahepatic metastasis, and less future remnant liver) or relapses after surgery. Other eligibility criteria included good physical status with an Eastern Co-operative Oncology Group (ECOG) performance status score of 0C2, a ChildCPugh score of 5C6, and no severe comorbidities. The patients previously treated with other chemotherapy regimens or immunotherapies were excluded. Detailed information.