Advances in liver cancer treatment: Levatinib combined with TACE can improve the survival rate of liver cancer patients

Introduction: TACE is an interventional treatment method, the full name of transhepatic artery intubation chemotherapy embolism, is currently the main non-surgical treatment method for the treatment of advanced liver cancer. In patients treated with ovatinib, the addition of TACE can prolong the patient's life and improve survival.

In the Phase 3 LAUNCH trial, levatinib combined with transarterial chemoembolization (TACE) significantly improved survival in patients with advanced hepatocellular carcinoma (HCC) compared with lenvatinib (Lenvima, levatinib) monotherapy.

The median overall survival of patients receiving combination therapy was 17.8 months, compared with 11.5 months in the lovatinib group. Similarly, median progression-free survival was also more favorable for the combination treatment group: 10.6 months vs 6.4 months.

Dr. Anthony B. El-Khoueiry of the NORRIS Comprehensive Cancer Center in Los Angeles said the findings were "interesting," and he praised the researchers who conducted the study. "This reinforces the feasibility of combining liver-directed therapy and systemic therapy," he said. However, this will not change the standard of treatment in the United States. ”

He added: "Systemic therapy is not the standard of treatment, and the design of this study does not best answer the question of whether increasing liver-directed therapy in advanced HCC improves prognosis."

The LAUNCH study involved 338 patients with early-stage advanced HCC from 12 hospitals in China who were randomly assigned to the lorvatinib TACE treatment group (n = 170) and the levatinib monotherapy group (n = 168).

TACE treatment is carried out on the 1st day after receiving levatinib treatment, depending on the weight of the patient, the dose of levatinib is 8 mg or 12 mg once a day.

Most patients are aged 60 years or younger, with a median age of 54 to 56 years. Most patients are male and have hepatitis B.

The median follow-up time of the combination treatment group and the lorvatinib group was 18.4 months and 17.0 months, respectively, and the results of the study showed that the overall survival of the combination treatment group was significantly improved at 17.8 months, compared with 11.5 months in the levatinib group. Median progression-free survival (PFS) was also significantly prolonged, at 10.6 months and 6.4 months, respectively.

The overall response rates in the combination treatment group and the levatinib group were 54.1% and 25.0%, respectively, and 1 complete response was observed in each study cohort. The complete response rates were 2.9% and 0.6%, respectively; Partial response rates were 51.2% and 24.4%, respectively; The stability rates were 40.0% and 48.2%, respectively; The rates of disease progression were 5.9% and 26.8%, respectively; Disease control rates were 94.1 percent and 73.2 percent, respectively.

Grade 3-4 adverse events occurred more frequently in the combination therapy group than in the levatinib group, including elevated liver enzymes and elevated ALT (alanine transaminases) (17.6% vs 1.2%); Elevated AST (aspartate aminotransferase) (22.9% vs. 1.8%); and hyperbilirubinemia (9.4% vs. 3.0%).

Subgroup analyses showed that in most subgroup analyses, the combination treatment group had better overall and progression-free survival. Multivariate analysis also found that portal vein cancer trombs and treatment allocation were independent risk factors for overall survival, and age, portal vein cancer embolus and treatment allocation were independent risk factors for progression-free survival.

Dr El-Khoueiry noted that the LAUNCH trial has several limitations, one of which is heterogeneity and potential imbalance in patient populations. "There is limited information about the burden and distribution of extrahepatic disease, he explains. Another limitation is that most young people have hepatitis B, limiting the broad applicability of the findings and potentially having an impact on low drug discontinuation rates. ”

Levatinib is a multi-target inhibitor, and in February 2015, the FDA approved levatinib for the treatment of advanced thyroid cancer; In May 2016, the FDA approved levatinib in combination with everolimus for the treatment of advanced renal cell carcinoma with failed anti-angiogenesis drugs; In September 2018, levatinib was launched in China for the treatment of unresectable hepatocellular carcinoma that had not previously received systemic therapy.

Despite the limitations of the trial, the results of the trial demonstrated that ovatinib combined with TACE could improve survival in patients, providing patients with a new treatment option and a new way of thinking for healthcare workers.