Important Clinical Factors in Sequential Therapy Including Lenvatinib against Unresectable Hepatocellular Carcinoma

Abstract

<b><i>Background/Aim:</i></b> We evaluated clinical factors related to improved prognosis of unresectable hepatocellular carcinoma patients (u-HCC), who were treated with tyrosine kinase inhibitor (TKI) sequential therapy, including lenvatinib (LEN). <b><i>Materials/Methods:</i></b> We enrolled 84 u-HCC cases treated with TKIs including LEN from March 2018 to January 2019 (median age 71 years, 63 males, Child-Pugh score (CPS) 5/6/7 = 62/21/1, tumor-node-metastasis stage of Liver Cancer Study Group of Japan 6th (TNM-LCSGJ) II/III/IVa/IVb = 12/30/5/37, Barcelona Clinic Liver Cancer stage B/C = 33:51). Clinical findings at introduction of the initial TKI were retrospectively evaluated. <b><i>Results:</i></b> The median albumin-bilirubin (ALBI) score at introduction of the initial TKI (sorafenib [SOR]/LEN = 80/4) was –2.56, and the past number of transarterial catheter chemoembolization was 3 (IQR: 2–5) (second-line: regorafenib [REG]/LEN/SOR = 31/49/4, third-line: LEN/REG = 31:1). The total period of administration with TKIs showed a good relationship with overall survival (OS) (<i>r</i> = 0.946, 95% confidence interval [CI]: 0.918–0.965, <i>p</i> < 0.001). The prognosis of the entire cohort was good (estimated median survival time: 46.4 months, 1-/2-/3-year OS rate [OSR] = 87.7/63.0/57.2%). A modified-ALBI grade (mALBI) of 2b (ALBI score >–2.27) was the only significant factor at the start of the initial TKI for poor prognosis (hazard ratio 2.319, 95% CI: 1.064–5.052, <i>p</i> = 0.034), while CPS (≥6) was not. Although there was no significant difference in TNM-LCSGJ (<i>p</i> = 0.213), the prognosis of patients with mALBI 1/2a (<i>n</i> = 66) showed better prognosis as compared to those with mALBI 2b (<i>n</i> = 18) (1-year/2-year/3-year OSR = 89.1/69.8/66% vs. 82.4/47.1/23.5%, <i>p</i> = 0.029). <b><i>Conclusion:</i></b> Good hepatic function (mALBI 1/2a) at introduction of the initial TKI is a requirement for improved prognosis of u-HCC undergoing TKI sequential therapy.

Favorable radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma

“…Physicians sometimes reduce lenvatinib doses due to lenvatinib-related AEs. 4,[14][15][16][17][22][23][24][25][26] In the present study, the most frequent cause that led to dose reduction or discontinuation of lenvatinib within 6 weeks was appetite loss (72.5%), and the median 2-6 W-RDI (69.6%) was significantly lower than the median 0-2 W-RDI (100%) due to the dose reduction or temporary interruption of lenvatinib. Hiraoka et al reported that appetite loss was an important AE in lenvatinib treatment for discontinuation clinically.…”

“…There have been several reports on the evaluation of antitumor response to lenvatinib using initial imaging, which were assessed from 4 to 8 weeks after lenvatinib introduction, in clinical practice. [14][15][16][17][22][23][24][25][26] These reports showed ORRs of 29.4-45.0% and DCRs of 60.0-93.0%. Similarly, the present study showed that relative to the image at baseline, the 6 W-ORR and 6 W-DCR were 50.0% and 90.0%, respectively.…”

“…4,8 However, in real-world practice, some patients with a Child-Pugh score of 7 received lenvatinib treatment under careful management by HCC treatment specialists, in cases that had no other effective therapy options available. [14][15][16][17] Patients who were not evaluated for radiological antitumor response to lenvatinib treatment by CE-CT for any reason (n = 6) and those who were observed for <6 weeks (n = 4) were excluded. The remaining patients (n = 40) were enrolled in the present study and underwent retrospective evaluation of their outcomes.…”

Nutritional Index as Prognostic Indicator in Patients Receiving Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma

“…Thus, if possible, it is important to introduce TKI drug treatment for u-HCC patients with better hepatic functional reserve first, in order to increase the possibility of sequential TKI treatments as postprogression therapy to improve OS. In fact, better hepatic function has been reported to be the only significant factor for sequential TKI therapy in u-HCC patients [32,33]. Those reports also suggested that the most suitable factor for showing hepatic function was an ALBI score of −2.53 [32] or −2.56 [33], which is approximate to the present cut-off for the best ALBI grade of 1 (−2.60).…”

“…In fact, better hepatic function has been reported to be the only significant factor for sequential TKI therapy in u-HCC patients [32,33]. Those reports also suggested that the most suitable factor for showing hepatic function was an ALBI score of −2.53 [32] or −2.56 [33], which is approximate to the present cut-off for the best ALBI grade of 1 (−2.60). Additionally, mALBI grade 2a (≤-2.27) has been suggested to be the lowest acceptable grade for introducing not only any TKI as first-line therapy but also LEN at any time to improve OS [28,33].…”