A groundbreaking phase II clinical trial has unveiled promising results in the fight against advanced hepatocellular carcinoma (HCC) by combining three therapeutic approaches: transcatheter arterial chemoembolization (TACE), lenvatinib, and tislelizumab. This triple therapy regimen targets HCC patients classified under the Barcelona Clinic Liver Cancer (BCLC) stage C, a category associated with advanced and typically unresectable tumors. The study, recently published in BMC Cancer, highlights a compelling improvement in objective response rates and survival outcomes, marking a significant milestone in liver cancer treatment strategies.
Hepatocellular carcinoma remains one of the most lethal malignancies worldwide, often diagnosed at stages too advanced for surgical intervention. Patients categorized within BCLC stage C face limited options, as systemic therapies frequently offer modest benefits. The innovative therapeutic combination explored in this study leverages the complementary mechanisms of locoregional and systemic treatments, aiming to overcome tumor resistance and improve clinical outcomes.
The clinical trial enrolled 31 patients diagnosed with advanced unresectable HCC. Initial treatment involved TACE, a minimally invasive procedure designed to deliver chemotherapy directly to liver tumors while obstructing their blood supply. This locoregional intervention was immediately followed by administration of lenvatinib, a multi-kinase inhibitor known to disrupt tumor angiogenesis and proliferation, and tislelizumab, a novel anti-PD-1 monoclonal antibody that reactivates anti-tumor immune responses.
Patients in the trial received tislelizumab intravenously every 21 days at a dose of 200 mg, while lenvatinib was administered daily at 8 or 12 mg, adjusting for patient-specific factors such as weight. The study’s primary endpoint was the objective response rate (ORR), assessed through modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints encompassed safety evaluations, overall survival (OS), progression-free survival (PFS), time to progression (TTP), duration of response (DOR), and the exploration of biomarkers such as the systemic immune-inflammation index (SII) to predict therapeutic efficacy.
Remarkably, the triple therapy demonstrated an ORR of 74.2%, a substantial improvement compared to historical controls treated with monotherapies or dual treatment regimens. Additionally, the disease control rate (DCR) reached an impressive 87.1% per mRECIST criteria, reflecting not only tumor shrinkage but also stabilization. These outcomes suggest a synergistic effect of combining local chemoembolization with systemic immunomodulation and targeted inhibition.
Median overall survival was reported at 12.6 months, while median progression-free survival extended to 6.5 months. Notably, the median time to progression observed was 8.2 months, and the median duration of response lasted 7.3 months. These metrics indicate a meaningful extension in survival and tumor control, offering hope to patients traditionally facing dismal prognoses under current standard care.
Safety profiles were carefully monitored and remained within manageable levels. Treatment-related adverse events (TRAEs) were documented in 64.5% of patients; however, most were grade 1 or 2, indicating mild to moderate severity. Serious adverse events of grade 3 or higher occurred in 19.4% of participants, underscoring the necessity for vigilant clinical monitoring but affirming an acceptable tolerability of the regimen.
The study also explored the prognostic significance of systemic immune-inflammation index (SII), a composite marker derived from peripheral blood parameters reflecting the balance of immune and inflammatory responses. Patients presenting with lower baseline SII exhibited superior overall survival and progression-free survival, highlighting SII’s potential as a predictive biomarker to tailor personalized treatment plans and optimize outcomes.
The mechanistic rationale of this triple combination stems from each modality’s distinct but complementary action against HCC. TACE initiates localized cytotoxicity while potentially exposing tumor antigens. Lenvatinib’s anti-angiogenic effects disrupt the tumor microenvironment, thereby inhibiting vascular support essential for tumor growth. Meanwhile, tislelizumab unleashes immune-mediated tumor cell elimination by blocking the PD-1 immune checkpoint pathway, thus enhancing the host’s anti-cancer immunity.
This study represents a crucial advancement in oncologic therapeutics by integrating locoregional and systemic strategies with immune checkpoint blockade. The encouraging clinical results provide a foundation for larger-scale, randomized controlled trials that may establish this triple therapy as a new standard of care for patients with advanced HCC, particularly those ineligible for surgical resection.
The promising outcomes also underscore the importance of biomarker-driven treatment personalization. Utilizing indices like SII could refine patient selection, guide treatment intensity, and ultimately improve survival rates in a disease notorious for therapeutic resistance. Future research will aim to validate these findings, explore mechanisms underpinning therapy resistance, and develop next-generation combination therapies.
Despite the inherent challenges posed by the complex biology of hepatocellular carcinoma, this early-phase study’s results invigorate the field with hope. They emphasize the power of a multifaceted approach that exploits tumor vulnerabilities across biological domains, combining cytotoxic, anti-angiogenic, and immunotherapeutic effects in a cohesive treatment paradigm.
In conclusion, the combination of TACE, lenvatinib, and tislelizumab offers a potent therapeutic option for patients with advanced, unresectable HCC. The phase II clinical trial demonstrates not only a high objective response rate but also an acceptable safety profile, paving the way for more extensive studies and potential paradigm shifts in managing this challenging malignancy. With continued investigation, this approach could significantly improve survival and quality of life for countless patients worldwide.
ClinicalTrials.gov records identify this study under the identifier NCT05131698, reflecting its rigorous protocol and ethical oversight. As the oncology community awaits further data, this pioneering research reinforces the promise of combination therapies and precision medicine in transforming liver cancer treatment.
Subject of Research: Advanced unresectable hepatocellular carcinoma treatment through combination therapy involving TACE, lenvatinib, and tislelizumab.
Article Title: Preliminary experience of lenvatinib, tislelizumab and transcatheter arterial chemoembolization for BCLC stage C hepatocellular carcinoma: a phase II study.
Article References:
Nong, X., Yao, Y., Xie, J. et al. Preliminary experience of lenvatinib, tislelizumab and transcatheter arterial chemoembolization for BCLC stage C hepatocellular carcinoma: a phase II study. BMC Cancer 25, 1631 (2025). https://doi.org/10.1186/s12885-025-15016-9
Image Credits: Scienmag.com
DOI: https://doi.org/10.1186/s12885-025-15016-9
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