TRIPLET combined with microwave ablation: A novel treatment for advanced hepatocellular carcinoma

Abstract

This editorial comments on a study by Zuo et al. The focus is on the efficacy of hepatic arterial infusion chemotherapy combined with camrelizumab and apatinib (the TRIPLET regimen), alongside microwave ablation therapy, in treating advanced hepatocellular carcinoma (HCC). The potential application of this combination therapy for patients with advanced HCC is evaluated.

Key Words: Microwave ablation; Hepatic arterial infusion chemotherapy; Apatinib; Camrelizumab; Hepatocellular carcinoma

Core Tip: This article examines the efficacy of combining microwave ablation with the TRIPLET regimen in patients with advanced hepatocellular carcinoma. While both treatments show promise individually, their combined efficacy and safety require further clinical investigation.

INTRODUCTION

Globally, primary liver cancer ranks as the sixth most common cancer diagnosis and the third leading cause of cancer-induced mortality, with hepatocellular carcinoma (HCC) accounting for 75%-80% of these cases[1]. Hepatic arterial infusion chemotherapy (HAIC) employing a combination of oxaliplatin, fluorouracil, and folinic acid (FOLFOX) effectively reduces intrahepatic tumor load by delivering chemotherapeutic agents directly to the arteries supplying the tumor[2]. Camrelizumab, a programmed death receptor 1 inhibitor, has been approved for the treatment of liver cancer[3]. Apatinib, the first highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor 2 in China, has shown efficacy in patients with advanced HCC[4].

The combination of HAIC with camrelizumab and apatinib, known as the TRIPLET regimen, has demonstrated efficacy in several studies for the treatment of advanced HCC[5]. Additionally, microwave ablation (MWA) is widely used as an effective local treatment for HCC and may potentially eliminate residual lesions after the TRIPLET regimen. However, the therapeutic efficacy of combining the TRIPLET regimen with MWA has yet to be thoroughly investigated.

In this editorial, we review and analyze the study by Zuo et al[6], published in the World Journal of Gastrointestinal Oncology, which explores this combination treatment.

EFFICACY

In their study, Zuo et al[6] divided patients into two groups to assess changes and treatment efficacy through detailed clinical follow-up and imaging data. The patients were categorized into the TRIPLET (T-A) group with 122 cases and the TRIPLET combined with MWA (T-M) group with 95 cases. Two statistical methods were used to make the study more rigorous, but the results were consistent. After a propensity score matchin, the study compared the outcomes of the T-A group with those of the T-M group, yielding the following results.

The objective response rate (ORR) of the T-M group (85.4%) was significantly higher than that of the T-A group (65.9%; P < 0.001). The 1-year, 2-year, and 3-year cumulative overall survival (OS) rates of the T-M group were 98.7%, 93.4%, and 82.0% respectively, while those of the T-A group were 85.1%, 63.1%, and 55.0% respectively (HR = 0.22; 95%CI: 0.10-0.49; P < 0.001). Safety is also an issue to be focused on. The incidence of major complications in the T-A group was 4.9% (6/122), and that in the T-M group was 5.3% (5/95), with P = 1.000, suggesting that there was no significant difference in safety between the T-M and T-A groups. These outcomes indicate that the T-M approach provides better ORR and OS benefits than the T-A regimen.

The therapeutic rationale for the T-M therapy likely stems from the advantages offered by MWA, such as the ability to target larger treatment areas and shorter treatment times[7], which effectively eliminate residual lesions after the TRIPLET regimen in advanced HCC. However, the precise mechanisms behind these benefits are not yet fully understood, necessitating further clinical studies in the future.

SHORTCOMINGS

As the authors themselves acknowledge, the study has a few limitations. First, this was a retrospective study with a small number of patients and a relatively short retrospective follow-up period. This calls for prospective randomized controlled trials to validate the findings. Secondly, the primary cause of HCC in China is hepatitis B virus infection, whereas in Western countries, it is often alcohol consumption. This raises questions about the applicability of the T-M protocol in different geographic and etiologic contexts. It is worth noting that this study addresses MWA and the results may not be generalisable to thermal ablation in general.

Additionally, the study notes that most patients undergoing MWA were under 70 years old. Since many elderly patients may not tolerate MWA well, further research is needed to determine the efficacy of this treatment for older patients with HCC.

Financial considerations also play a crucial role. The TRIPLET regimen combined with MWA is likely to be more costly than the TRIPLET regimen alone. Therefore, it is important to investigate this combined approach while considering financial factors and the varying healthcare policies of different countries.

CONCLUSION

The combination of MWA therapy with the TRIPLET regimen (HAIC with camrelizumab and apatinib) significantly improves OS. This approach could represent a promising new treatment option for these patients.