Presently, there are no therapeutic options for unresectable hepatocellular carcinoma (u-HCC) patients who are intolerant to sorafenib or regorafenib failure. There have been no reports with detailed clinical findings of lenvatinib (LEN), a newly developed first-line tyrosine kinase inhibitor (TKI), obtained in real-world practice. We aimed to elucidate the therapeutic efficacy of LEN.
For treatment of unresectable hepatocellular carcinoma (u?HCC), tyrosine kinase inhibitors (TKIs), such as sorafenib (SOR) and regorafenib (REG), have been introduced. SOR was developed as a first?line agent for u?HCC, while REG is used as second?line therapy in patients who show good tolerability and progressive disease (PD) with SOR.
Recently, lenvatinib (LEN), a new TKI, has become available as a first?line drug for u?HCC. However, though the number of TKIs for u?HCC has increased, there is presently no therapeutic option for patients with SOR failure or who show intolerability for SOR as well as a failure with REG, indicating an important and practical unmet need.
Following the introduction of LEN in clinical practice in Japan in March 2018, the drug has been used in real?world practice not only for TKI?naïve but also for TKI?experienced patients as second? or third?line treatment.
Adverse events (AEs) associated with LEN treatment
On the other hand, therapeutic response and adverse events (AEs) associated with LEN treatment for u?HCC patients with and without a past history of TKI have not been elucidated. In the present study, we analyzed the clinical features of patients who received LEN treatment for u?HCC for therapeutic response and AEs.
From March to August 2018, 105 u-HCC patients were treated with LEN. Following exclusion of those who started with a reduced LEN dose and/or had a short observation period (<2 weeks), 77 patients (72.0 ± 8.9 years, 59 males, 8 mg/12 mg = 49/28.
Liver Cancer Study Group of Japan 6th [LCSGJ]-TNM stage II/III/IVa/IVb = 8/28/4/37, and American Joint Committee on Cancer/Union for International Cancer Control 8th [AJCC/UICC]-TNM stage IB:II:IIIA:IIIB:IVA:IVB = 2:27:6:5:9:28) were divided into two groups (TKI naïve [n = 33] and TKI experienced [n = 44], including 11 with regorafenib history). Therapeutic response was evaluated using mRECIST. Clinical data were retrospectively evaluated.
There were significant differences in age (74.6 ± 11.2 vs 70.0 ± 5.9 years, P = 0.040), LCSGJ-TNM (II:III:IVa:IVb = 8:12:1:12 vs 0:16:3:25, P = 0.006), and AJCC/UICC-TNM (IB:II:IIIA:IIIB:IVA:IVB = 2:17:1:1:4:8 vs 0:10:5:4:5:20, P = 0.028), while hepatic reserve function, adverse event (AE) profiles, and progression-free survival (89.7%/80.4% vs 90.5%/80.1%, P = 0.499) and overall survival (96.7%/96.7% vs 100%/92.3%, P = 0.769) after 4 and 12 weeks were not significantly different between the TKI-naïve and TKI-experienced groups.
Overall response rate and disease control rate at 4 weeks (n = 52) were 38.5% and 80.8%, respectively, and 32.4% and 70.3%, respectively, at 12 weeks (n = 37). A significant decline in log10 AFP from the baseline to 4 weeks after introducing LEN was observed in patients with PR and SD (2.047 ± 1.148 vs 1.796 ± 1.179, P < 0.001).
Regardless of past TKI therapy, therapeutic response and AEs after introducing LEN were similar. LEN may be an important treatment for the present unmet need regarding TKI treatment against u-HCC.