Objective: We assessed the efficacy and safety of transarterial chemoembolization (TACE) in combination with lenvatinib plus programmed death receptor-1 (PD-1) signaling inhibitors (camrelizumab or sintilimab) in unresectable hepatocellular carcinoma (uHCC). Methods: In this retrospective study, patients with uHCC were pretreated with lenvatinib for 1 to 2 weeks before TACE. Camrelizumab or sintilimab were initially administered intravenously in 1 week after TACE of a 21-day cycle. Primary objectives were objective response rate (ORR) and disease control rate (DCR) by modified Response Evaluation Criteria in Solid Tumors (mRECIST). The secondary endpoints included the progression-free survival (PFS), overall survival (OS), and toxicity. Results: Between March 5, 2019 and February 30, 2021, 53 patients were screened for eligibility. At data cutoff, 35.8% of patients remained on treatment. Median follow-up was 15.4 months. Confirmed ORR in the 51 evaluable patients was 54.9% (95% CI 41.4%-67.7%). DCR was 84.3% (95% CI 72.0%-91.8%). Median PFS was 8.5 months (95% CI 6.4 to 10.6 months). The median OS was not estimable. Grade ≥3 treatment-related adverse events occurred in 32.1% of patients. No new safety signals were identified. Conclusion: TACE in combination with lenvatinib plus anti-PD-1 inhibitors may have promising antitumor activity in uHCC. Toxicities were manageable, with no unexpected safety signals.

Background: Patients with advanced intrahepatic cholangiocarcinoma (iCCA) have a poor prognosis and a substantial unmet clinical need. The study was aimed to investigate the efficacy and safety of sintilimab combined with lenvatinib for advanced iCCA in second-line setting.Methods: The patients at multiple centers, who progressed after the first-line chemotherapy or could not tolerate chemotherapy, were treated with the combination of sintilimab plus lenvatinib. The primary endpoint was time to progression (TTP), and the secondary endpoints included tumor objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Prognostic factors were analyzed using Cox regression analysis.Results: A total of 41 patients with advanced iCCA were enrolled for this multi-center observational study. Under a median follow-up of 12.1 months, the median age was 59 years (range, 33–75 years). Sixteen patients died of disease progression, with a median TTP of 6.6 months (95% CI, 4.9–8.3). ORR and DCR were 46.3% and 70.3%, respectively. The patients with PD-L1 TPS ≥10% reported a significantly higher ORR compared to those with PD-L1 TPS <10%, 93.8% (15/16) vs. 16.0% (4/25), p<0.001. The median TTP was significantly improved in patients with PD-L1 TPS ≥10%, 16.9 months (95% CI, 7.5–26.3) vs. 4.1 months (95% CI, 1.8–6.4), p=0.001. Attaining treatment response predicts favorable TTP in a multivariate Cox model. Treatment-emergent adverse events occurred with 70.3% probability, and no treatment-related death had been reported.Conclusion: The combination of sintilimab plus lenvatinib is effective and well tolerated for advanced iCCA in the second-line setting. PD-L1 TPS expression may predict the efficacy of the combination therapy. Further investigation is warranted to investigate this combination regimen in advanced iCCA.

Background and aims: Hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) predicts a poor prognosis. The aim of the present study was to evaluate the efficacy and safety of using lenvatinib and camrelizumab combined with transarterial chemoembolization (TACE) to treat HCC with PVTT.Methods: This was a single‐arm, open‐label, multicenter, and prospective study. Eligible patients with advanced HCC accompanied by PVTT were enrolled to receive TACE combined with lenvatinib and camrelizumab. The primary endpoint was progression‐free survival (PFS), while the secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.Results: Between April 2020 and April 2022, 69 patients were successfully enrolled. With a median follow‐up time of 17.3 months, the median age of the patient cohort was 57 years (range: 49–64 years). According to modified Response Evaluation Criteria in Solid Tumors, the ORR was 26.1% (18 partial responses [PRs]) and the DCR was 78.3% (18 PRs, 36 stable diseases [SDs]). The median PFS (mPFS) and median OS (mOS) were 9.3 and 18.2 months, respectively. And tumor number >3 was identified as an adverse risk factor for both PFS and OS. The most common adverse events across all grades included fatigue (50.7%), hypertension (46.4%), and diarrhea (43.5%). Twenty‐four patients (34.8%) experienced Grade 3 toxicity that was relieved by dose adjustment and symptomatic treatment. No treatment‐related deaths occurred.Conclusions: TACE combined with lenvatinib and camrelizumab is a well‐tolerated modality treatment with promising efficacy for advanced HCC with PVTT.

BACKGROUND Hepatocellular carcinoma (HCC) patients complicated with portal vein tumor thrombus (PVTT) exhibit poor prognoses and treatment responses. AIM To investigate efficacies and safety of the combination of PD-1 inhibitor, transcatheter arterial chemoembolization (TACE) and Lenvatinib in HCC subjects comorbid with PVTT. METHODS From January 2019 to December 2020, HCC patients with PVTT types I-IV were retrospectively enrolled at Beijing Ditan Hospital. They were distributed to either the PTL or TACE/Lenvatinib (TL) group. The median progression-free survival (mPFS) was set as the primary endpoint, while parameters like median overall survival, objective response rate, disease control rate (DCR), and toxicity level served as secondary endpoints. RESULTS Forty-one eligible patients were finally recruited for this study and divided into the PTL (n = 18) and TL (n = 23) groups. For a median follow-up of 21.8 months, the DCRs were 88.9% and 60.9% in the PTL and TL groups (P = 0.046), res-pectively. Moreover, mPFS indicated significant improvement (HR = 0.25; P < 0.001) in PTL-treated patients (5.4 months) compared to TL-treated (2.7 months) patients. There were no treatment-related deaths or differences in adverse events in either group. CONCLUSION A triplet regimen of PTL was safe and well-tolerated as well as exhibited favorable efficacy over the TL regimen for advanced-stage HCC patients with PVTT types I-IV.

Objective: To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment. Design: Systematic review. Data sources: PubMed and Embase until December 2020 and manually searched references from eligible articles. Eligibility criteria for study selection: The development, validation, or updating of prognostic models of patients with HCC after systemic treatment. Results: The systematic search yielded 42 eligible articles: 28 articles described the development of 28 prognostic models of patients with HCC treated with systemic therapy, and 14 articles described the external validation of 32 existing prognostic models of patients with HCC undergoing systemic treatment. Among the 28 prognostic models, six were developed based on genes, of which five were expressed in full equations; the other 22 prognostic models were developed based on common clinical factors. Of the 28 prognostic models, 11 were validated both internally and externally, nine were validated only internally, two were validated only externally, and the remaining six models did not undergo any type of validation. Among the 28 prognostic models, the most common systemic treatment was sorafenib (n = 19); the most prevalent endpoint was overall survival (n = 28); and the most commonly used predictors were alpha-fetoprotein (n = 15), bilirubin (n = 8), albumin (n = 8), Child–Pugh score (n = 8), extrahepatic metastasis (n = 7), and tumor size (n = 7). Further, among 32 externally validated prognostic models, 12 were externally validated > 3 times. Conclusions: This study describes and analyzes the prognostic models developed and validated for patients with HCC who have undergone systemic treatment. The results show that there are some methodological flaws in the model development process, and that external validation is rarely performed. Future research should focus on validating and updating existing models, and evaluating the effects of these models in clinical practice. Systematic review registration: PROSPERO CRD42020200187.