A multicenter study found that using lenvatinib for initial treatment helped to increase survival in patients with stage B2 hepatocellular carcinoma.
Barcelona Clinic Licer Cancer (BCLC) stage B2 hepatocellular carcinoma (HCC) treated initially with lenvatinib (Lenvima) experienced increased survival, according to results of a multicenter observational study that were presented at the 2022 Gastrointestinal Symposium.
As the standard treatment for these patients was transarterial chemoembolization (TACE), the researchers emphasized that it may not be suitable for patients beyond the up-to-7 criteria, which is when the number of tumors is added to the diameter of the largest tumor by centimeter. If the sum is 7 or less, the disease meets the criteria. Patients whose disease did not meet this standard may have insufficient efficacy and decline of liver function.
Investigators sought to determine whether levatinib was efficacious for patients aged 20 years or older diagnosed with stage B2 HCC, naïve to TACE and systemic chemotherapy and who had preserved organ function.
The primary endpoint—which was met—was 1-year survival rate with a threshold of 60% and an expected survival rate of 78% based on previous reports of TACE.
Thirty-one eligible patients (median age, 77; range: 57-86) were recruited during a 2-year enrollment period starting in June 2018, closing in June 2020. There was a follow-up period of 10 months. Data cut-off was April 2021.
Most of the patients were men (94%), with etiology of chronic liver disease being hepatitis B virus (3 patients), hepatitis C virus (6), alcohol abuse (9), and other (10). There were Child-Pugh scores of 5 and 6 for 20 and 11 patients, respectively. The median maximum tumor diameter was 36 mm (range: 10-135) and 8 patients had a tumor number of 10 or more. The median alpha-fetoprotein (AFP) level was 52.1 ng/mL (range: 2.4-49800).
The trial had a 1-year survival rate of 71.0% (90% CI: 68.4-73.6). Median overall survival was 17.0 months (95% CI, 15.3-19.2) and median progression-free survival was 10.4 months (95% CI, 6.6-13.8). The 2-year survival rate, however, was 32.3%. There was an objective response rate (ORR) of 22.6% according to RECIST1.1 and 70.0% according to mRECIST criteria.
The most common all-grade adverse events patients experienced were fatigue (68%), hypertension (65%), and anorexia (61%), aspartate aminotransferase (AST) increased (23%), alanine aminotransferase (ALT) increased (16%), and grade 3 or worse proteinuria (13%).
“No new safety profile was found,” the researchers wrote in their poster presentation.
Treatment interruption was required in 61% of patients, and dose reduction in 81%. Median relative dose intensity was 61.8% (range: 7.5-100). Out of 24 patients at the time of analysis, 17 (55%) discontinued lenvatinib due to disease progression, nine (29%) due to adverse events, and two (6%) due to conversion to curative treatments. There was one patient death due to unknown reasons, though the patient had a partial response to the treatment.
For post-study treatment, 11 patients were administered systemic chemotherapy, six were administered TACE and one was given transarterial infusion.
“Randomized controlled trials (comparing) lenvatinib and TACE for patients with BCLC sub-stage B2 HCC are warranted, and systemic chemotherapy preceding TACE will be a standard treatment strategy,” the investigators wrote.
Kobayashi S, Numata K, Fukushima T, et al. A prospective observational study of lenvatinib as an initial treatment for patients with intermediate-stage hepatocellular carcinoma. J Clin Oncol. 2022;40(suppl4):412. doi:10.1200/JCO.2022.40.4_suppl.412