A prospective observational study of lenvatinib as an initial treatment for patients with intermediate-stage hepatocellular carcinoma.
Authors: Kobayashi Satoshi , Numata Kazushi , Fukushima Taito , Ueno Makoto , Moriya Satoshi , Chuma Makoto , Tsuruya Kota , Hirose Shunji , Kagawa Tatehiro , Hattori Nobuhiro , Matsunaga Kotaro , Watanabe Tsunemasa , Uojima Haruki , Hidaka Hisashi , Kusano Chika , Morimoto Manabu 
Published: January 2022

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Background: The standard treatment for intermediate stage hepatocellular carcinoma (HCC) has been transarterial chemoembolization (TACE); however, it might not be suitable for patients (pts) beyond the up-to-7 criteria because of its insufficient efficacy and decline of liver function. Conversely, lenvatinib has shown a good response rate in the phase III trial REFLECT and was considered promising as an initial treatment for patients with BCLC stage B2 HCC. Methods: We conducted a multicenter prospective observational study to evaluate the efficacy of lenvatinib as an initial treatment for pts aged 20 years or older, diagnosed with BCLC stage B2 HCC, naive to TACE, and with preserved organ function. The primary endpoint was a 1-year survival rate, with a threshold of 60% and an expected survival rate of 78% based on previous reports of TACE. With a one-sided alpha error of 5% and a power of 70%, 25 pts were recruited over an enrollment period of 2 years and a follow-up period of 10 months. Results: Enrollment began in June 2018 and was closed with 31 eligible pts enrolled by June 2020. Data cut-off was done in April 2021. Patient characteristics are as follows: the median age was 77 years (range: 57–86); 94% of the pts were male; the etiology of chronic liver disease was hepatitis B virus, hepatitis C virus, alcohol abuse, and others in 3, 6, 9, and 10 pts, respectively; 20 and 11 pts had a Child-Pugh score of 5 and 6 points, respectively; the median maximum tumor diameter was 36 mm (range: 10–135); the number of pts with a tumor number of ≥10 was 8; and the median AFP level was 52.1 ng/mL (range: 2.4–49800). The 1-year survival rate was 71.0% (90% confidence interval [CI]: 68.4–73.6) and the primary endpoint was met. The median overall and progression-free survival was 17.0 months (95% CI, 15.3–19.2) and 10.4 months (95% CI, 6.6–13.8), respectively; the 2-year survival rate was 32.3%. The objective response rate according to RECIT1.1 and mRECIST was 22.6% and 70.0%, respectively. The common adverse events (AEs) were fatigue (68%), hypertension (65%), and anorexia (61%) in any grade, AST increased (23%), ALT increased (16%), and proteinuria (13%) in grade 3 or worse. Treatment interruption and dose reduction was required in 61% and 81% of the pts, respectively. The median relative dose intensity was 61.8% (range: 7.5–100). At the time of analysis, out of 24 pts, 17 (55%), nine (29%), and two (6%) discontinued lenvatinib due to disease progression, AEs, and conversion to curative treatments, respectively. One patient who showed partial response suddenly died during treatment due to unknown reasons. Systemic chemotherapy, TACE, and transarterial infusion therapy was administered in 11 (38%), six (21%) and one (3%) as a post study treatment, respectively. Conclusions: Our study indicates that initial treatment using lenvatinib prolongs the survival of pts with BCLC stage B2 HCC.