Lenvatinib-TACE combo a new first-line treatment alternative for advanced HCC?

Audrey Abella
23 Feb 2022
Lenvatinib-TACE combo a new first-line treatment alternative for advanced liver cancer?

In individuals with advanced hepatocellular carcinoma (HCC), the combination of transarterial chemoembolization (TACE) and lenvatinib as first-line treatment led to improved survival outcomes as opposed to lenvatinib monotherapy, according to findings of the phase III LAUNCH* trial.

Most HCC patients are at the advanced stage at the time of diagnosis, rendering them unavailable for curative treatments such as transplantation, resection, and ablation, said Dr Ming Kuang from The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China, who presented the findings at ASCO GI 2022. “[This is] one of the major challenges of HCC treatment … and for these patients, systemic therapy is a major choice.”

Sorafenib has been the recommended systemic therapy for HCC but following the introduction of lenvatinib in 2018, the latter is now the most widely used first-line treatment for advanced HCC, noted Kuang. “However … tumour burden is a major threat to improvement with lenvatinib … [Hence, its] efficacy will need to be improved for better [disease] control.”

A potential strategy to enhance the efficacy of lenvatinib in this setting is to combine it with local therapy such as TACE. “TACE can reduce tumour burden in a very short time,” Kuang said, but post-TACE neovascularization may lead to tumour metastasis and recurrence. “[Nonetheless,] lenvatinib can inhibit angiogenesis and tumour cell proliferation … [As such,] the combination of these two treatments may provide a better choice than lenvatinib alone.”

The team sought to evaluate the efficacy and safety of lenvatinib, either alone or in combination with TACE, in 338 patients (median age 55 years, 80 percent male) who were randomized 1:1 to either arm. Participants had advanced primary HCC without any prior treatment or initial recurrent advanced HCC following radical resection. Lenvatinib was given orally within 3 days after randomization at an initial daily dose of 8 mg for patients weighing <60 kg or 12 mg for those weighing 60 kg. TACE was initiated a day after initial lenvatinib administration, then on-demand according to the condition of the tumour and liver function. [ASCO GI, abstract 380]

Median overall survival was significantly longer with lenvatinib-TACE vs lenvatinib alone (17.8 vs 11.5 months; stratified hazard ratio [HR] for death, 0.45), as was median progression-free survival (10.6 vs 6.4 months; HR, 0.43; p<0.001 for both).

Survival was also better with lenvatinib-TACE compared with lenvatinib alone in most of the evaluated subgroups, noted Kuang.

On multivariate analysis, it was determined that portal vein tumour thrombosis and treatment allocation were independent risks factors for both OS and PFS (p<0.0001 for all). Age also factored in as a risk factor for PFS (p=0.007).

In the lenvatinib monotherapy arm, objective response rate (ORR) and disease control rate (DCR) were 25 percent and 73 percent, respectively. In the combination arm, the respective ORR and DCR were higher (54 percent and 94 percent). Between-group comparisons yielded statistical significance (p<0.001) for both variables.

The better survival outcomes with the combination vs the monotherapy regimen was however countered by markedly higher rates of grade 3/4 adverse events (AEs) observed with the former vs the latter, such as increases in ALT/AST** levels (p<0.001 for both) and hyperbilirubinemia (p=0.014). Apart from these, the most notable AEs of any grade associated with the combination regimen were abdominal pain, nausea, fever, and vomiting (p<0.001 for all). “[Nonetheless, all AEs] disappeared after 2 weeks of treatment,” said Kuang.

“In conclusion, [our findings] showed that the combination of lenvatinib plus TACE can improve clinical outcomes in patients with advanced HCC,” said Kuang. “Lenvatinib-TACE thus represents a potential new first-line treatment option for [these patients and] may give us more hope in the future [for advanced HCC treatment].”


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