ObjectiveWe investigated lenvatinib plus programmed cell death-1 (PD-1) inhibitors as a first-line treatment for initially unresectable biliary tract cancer (BTC).MethodsIn this Phase II study, adults with initially unresectable BTC received lenvatinib (body weight ≥60 kg, 12 mg; <60 kg, 8 mg) daily and PD-1 inhibitors (pembrolizumab/tislelizumab/sintilimab/camrelizumab 200 mg or toripalimab 240 mg) every 3 weeks. Primary endpoints were objective response rate (ORR) and safety. Secondary endpoints included surgical conversion rate, disease control rate (DCR), event-free survival (EFS), overall survival (OS) and tumor biomarkers.ResultsAmong 38 enrolled patients, the ORR was 42.1% and the DCR was 76.3%. Thirteen (34.2%) patients achieved downstaging and underwent surgery, six of whom (46.2%) achieved a major pathologic response (n=2) or partial pathologic response (n=4) in the primary tumor. In total, 84.2% of patients experienced ≥1 treatment-related adverse event (TRAE), 34.2% experienced a Grade ≥3 TRAE and no treatment-related deaths occurred. After a median follow-up of 13.7 months the median EFS was 8.0 months (95% CI: 4.6–11.4) and the median OS was 17.7 months (95% CI: not estimable).ConclusionsLenvatinib plus PD-1 inhibitors showed promising anti-tumor efficacy in patients with initially unresectable BTC and was generally well tolerated.Clinical Trial Registrationwww.chictr.org.cn, ChiCTR2100044476.

Background & Aims Diabetes mellitus is known to negatively impact the outcome of liver transplant; however, data are scarce regarding risk of waitlist dropout and tumour recurrence in patients with hepatocellular carcinoma. We examined the impact of diabetes mellitus on the outcomes of candidates with hepatocellular carcinoma on an intention‐to‐treat basis. Methods Our study included 15 776 candidates with hepatocellular carcinoma diagnosis on the Scientific Registry of Transplant Recipients database from 2008 to 2015 to evaluate the risk of waitlist dropout, hepatocellular carcinoma recurrence and overall survival. Results There were more patients dropped out from the waiting list owing to patient disease deterioration or tumour progression in the diabetes mellitus group (15.1% vs 13.7%, P = 0.024). The mean waiting time was similar in the two groups (233 days vs 230 days, P = 0.631). The recurrence rate was higher in the diabetes mellitus group (9.0% vs 6.2%, P < 0.001); however, the mean time to recurrence in the two groups was similar (23.7 months vs 22.6 months, P = 0.371). Diabetes mellitus, tumours exceeding Milan criteria, and AFP >400 ng/mL were independent predictive factors for recurrence. On an intention‐to‐treat basis, diabetes mellitus was also an independent poor prognostic factor for overall survival; however, the overall survival was comparable with tumours beyond Milan criteria. Conclusions Diabetes mellitus was associated with poor survival outcomes and an increased risk of waitlist dropout and tumour recurrence rates in hepatocellular carcinoma patients. Those patients should be paid more attention to cardiovascular and oncological examination when determining waitlist and post‐transplant surveillance strategies.

Background Lenvatinib and programmed cell death-1 (PD-1) inhibitors have emerged as a novel treatment for patients with BTC. This study aimed to compare the efficacy and safety of triple therapy with lenvatinib, PD-1 inhibitors plus chemotherapy (LenP + C) and dual therapy with lenvatinib plus PD-1 inhibitors (LenP) in patients with unresectable or recurrent BTC. Methods BTC patients receiving LenP + C or LenP treatment between June 2020 and March 2022 were retrospectively analyzed. The primary outcome was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results Ninety-eight patients were included in the present study, and they were divided into the LenP + C group (n = 40) and LenP group (n = 58). The median PFS was 8.3 months in the LenP + C group, significantly longer than 4.5 months in the LenP group (HR = 0.471; 95% CI, 0.271–0.817; P = 0.007). Although no difference was found in ORR between the two groups (LenP + C, 42.5% vs. LenP, 27.6%, P = 0.125), the DCR was higher in the LenP + C group than in the LenP group (95.0% vs. 75.9%, P = 0.012). The median OS was comparable between the two groups (13.7 vs. 12.4 months, P = 0.749). Treatment-related adverse events were more frequently observed in the LenP + C group. The incidence of neutropenia (grade ⩾3) was higher in patients receiving triple therapy (15% vs. 2%, P = 0.035). Conclusions This study showed that treatment with lenvatinib and PD-1 inhibitors is safe and effective for advanced BTC. The combination of chemotherapy with lenvatinib and PD-1 inhibitors showed improved anti-tumor efficacy compared with lenvatinib and anti-PD-1 therapy, yet with more toxic effects.

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