Editor’s Note:

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most patients are diagnosed at intermediate or advanced stages. The formation of portal vein tumor thrombus (PVTT) is a significant indicator of advanced HCC, with over half of late-stage HCC patients presenting with PVTT. Especially VP4 type (main portal vein), these patients usually have a poor prognosis. Most phase III clinical trials have excluded these patients. Lenvatinib is a new multi-targeted small molecule inhibitor now approved for advanced HCC. In Asian populations, Lenvatinib combined with a PD-1 inhibitor has shown good antitumor activity and safety. Radiotherapy has also brought about positive outcomes for HCC patients with PVTT. The 13th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2023) was held in Seoul, Korea, from July 6-8, 2023. At the conference, the team from the affiliated Beijing Tsinghua Chang Gung Hospital, Tsinghua University, China, reported on a clinical study (Abstract Number: PE-117), exploring the preliminary efficacy and safety of Lenvatinib combined with a PD-1 inhibitor and radiotherapy in HCC patients with main portal vein tumor thrombus. Hepatology Digest invited Dr. Guangxin Li to share insights on the study and its clinical prospects.

Research Method:

Between March 1, 2018, and October 31, 2020, HCC patients with main portal vein tumor thrombus treated with Lenvatinib and PD-1 inhibitors (Pembrolizumab, Nivolumab, or Cemiplimab) combined with radiotherapy at Beijing Tsinghua Chang Gung Hospital were reviewed. The effectiveness was evaluated based on survival and PVTT remission rates, and safety was assessed by the incidence of key adverse events.

Research Results:

A total of 39 qualified HCC patients with VP4 type PVTT who received the triple combination therapy were included. The primary endpoint—2-year overall survival (OS) was 15.4%. Median OS and progression-free survival (PFS) were 9.4 months (range 2.3-57.1 months) and 4.9 months (range 1.4-36.1 months) respectively. The PVTT objective response rate (ORR) based on mRECIST criteria was 61.5%. The results showed that alpha-fetoprotein (AFP) level is an independent risk factor associated with OS, which normalized 3 months after radiotherapy. All adverse events were controlled, with no treatment-related deaths.

Research Conclusion:

In HCC patients with VP4 type PVTT, Lenvatinib combined with PD-1 inhibitors and radiotherapy has significant therapeutic effects and controllable safety, making it a potential treatment choice for advanced HCC.

Expert’s Review:

HCC patients with PVTT generally have worse outcomes than those without tumor thrombus. Currently, there are notable differences between Western and Eastern treatment philosophies. Western mainstream opinion mainly focuses on systemic drug treatment, while guidelines in China, Japan, and Korea mention a broader range of treatments including surgery, localized treatments such as TACE, HAIC, and radiotherapy. The findings presented at this APPLE conference offer new insights for treating HCC with PVTT.

1. Radiotherapy is a highly effective treatment for PVTT, especially when combined with targeted and immunotherapy, with an ORR of 61.4% in this study.

2. Combining radiotherapy with targeted immunotherapy for PVTT merits further prospective studies with larger samples, aiming to gather more robust evidence.

3. Elevated baseline AFP levels that decrease shortly after combined treatment predict better overall outcomes, a key finding in our study.

In summary, the study suggests a multidisciplinary approach might be more effective for advanced HCC. The prognosis for HCC patients with PVTT may be grim, but many beneficial attempts have started, and more efforts will be made in the future. As the saying goes, “The road ahead is long,” but we will keep exploring. With our collective efforts, we believe the survival of HCC patients with PVTT will see significant improvement in the future.

Reference: Guangxin Li, Gong Li et al. Effectiveness and safety of lenvatinib, a PD-1 inhibitor plus radiotherapy, in patients with hepatocellular carcinoma with main portal vein tumour thrombus: Real-world experience from a tertiary center. APPLE 2023 Abstract PE-117