The combination of TACE and lenvatinib “represents a potential new first-line treatment option for patients with advanced HCC,” said study author Ming Kuang, MD, PhD, professor in hepatobiliary surgery and interventional ultrasound and director of the cancer center in the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
The combination of the two approaches was “safe and effective for patients with advanced hepatocellular carcinoma and demonstrated remarkable improvements in overall survival, progression-free survival, and overall response rate, as well as acceptable toxicity,” he said.
Patients receiving combination therapy achieved a median overall survival of 17.8 months, compared with 11.5 months in the lenvatinib arm (hazard ratio, 0.45; P < .001). Similarly, median progression-free survival also favored lenvatinib plus TACE: 10.6 months vs. 6.4 months (HR, 0.43; P < .001).
The study results were presented at the Gastrointestinal Cancers Symposium.
Discussing the abstract, Anthony B. El-Khoueiry, MD, from the University of Southern California, Norris Comprehensive Cancer Center, Los Angeles, said the results are “intriguing,” and he commended the researchers on carrying out this study.
“It reinforces the feasibility of combined liver directed and systemic therapy,” he said.
“However, it does not change the standard of care in the U.S.,” he cautioned.
“Systemic therapy backbone is not the standard of care, and the design of this study was not optimal to answer the question of whether the addition of liver-directed therapy in advanced HCC improves outcomes,” he added.
Dr. EL-Khoueiry pointed out that these new results from the LAUNCH trial contrast with two studies that looked at liver-directed plus a systemic therapy. Both of those previous studies used sorafenib, one utilizing Y-90 and the other conventional TACE.
Both of those studies were negative, he said. “But there were differences between these studies and LAUNCH.”
Aside from the fact that they used sorafenib and not lenvatinib, another difference was that the patient population of LAUNCH was younger than in the other two studies. In addition, most patients in the LAUCH trial had hepatitis B, and they received a higher number of TACE treatments than in the previous studies. “One can argue that maybe treatment selection was more optimal,” Dr. El-Khoueiry commented.
He also noted that “the control arm of lenvatinib underperformed, as sorafenib median overall survival in previous trials ranges from 13 to 15 months. We would have expected lenvatinib to perform at least as well or better.” (The median overall survival was 11.5 months).
Improved outcomes with combination therapy
The LAUNCH study involved 338 treatment-naive patients with advanced HCC from 12 hospitals in China who were randomly assigned to receive either lenvatinib plus TACE (n = 170) or lenvatinib alone (n = 168).
TACE was administered on day 1 following treatment with lenvatinib, which was administered at 8 mg or 12 mg once daily, depending on the patient’s weight.
The majority of patients were 60 years of age or younger, with a median age of 54-56 years. The majority of patients were male (81.8% in the combination group vs. 78.6% in the lenvatinib-alone group), and the majority had hepatitis B (87.1% vs. 85.7%).
At a median follow-up of 18.4 months for the lenvatinib-TACE group and 17.0 months for the lenvatinib group, the results showed a significantly improved overall survival of 17.8 months with the combination vs. 11.5 months for monotherapy (HR, 0.45; P < .001). Median progression-free survival (PFS) was also significantly longer, at 10.6 months vs. 6.4 months, respectively (HR, 0.43; P < .001).
The overall response rate was 54.1% vs. 25.0% (P < .001), and one complete response was observed in each study arm. The complete response rate was 2.9% vs. 0.6%; partial response rate, 51.2% vs. 24.4%; stable disease rate, 40.0% vs. 48.2%; and rate of disease progression, 5.9% vs. 26.8% for the lenvatinib-TACE group and lenvatinib monotherapy groups. The disease control rate was 94.1% vs. 73.2%.
Grade 3-4 adverse events that occurred more frequently in the lenvatinib-TACE group than in the lenvatinib group included increased liver enzymes, with increased ALT in 17.6% vs. 1.2%; increased AST in 22.9% vs. 1.8%; and hyperbilirubinemia in 9.4% vs. 3.0%.
“Subgroup analysis shows that the combination group had better overall survival and progression-free survival in most of the analyzed subgroups,” said Dr. Kuang. “Multivariate analysis also found that portal vein tumor thrombus and treatment allocation were independent risk factors of overall survival, and that age, portal vein tumor thrombus, and treatment allocation were independent risk factors of progression-free survival.”
Study limitations
In his discussion of the abstract, Dr. El-Khoueiry noted that the LAUNCH trial had several limitations, one being the heterogeneity of the patient population and potential imbalance. “There is limited information regarding extrahepatic disease burden and distribution,” he explained. “Another limitation is that the younger population – with the majority having hepatitis B – limits the broad applicability of the result and has a potential impact on the low rate of treatment discontinuation.”
This study received no industry funding. Dr. Kuang has disclosed no relevant financial relationships. Dr. El-Khoueiry reported relationships with ABL bio, Agenus, Astex, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, CytomX Therapeutics, Eisai, EMD Serono, Exelixis, Fulgent Genetics, Gilead Sciences, Merck, Pieris Pharmaceuticals, QED Therapeutics, and Roche/Genentech.
A version of this article first appeared on Medscape.com.