Therapeutic potential of lenvatinib for unresectable hepatocellular carcinoma in clinical practice: Multicenter analysis

Hiraoka, Atsushi; Kumada, Takashi; Kariyama, Kazuya; Takaguchi, Koichi; Itobayashi, Ei; Shimada, Noritomo; Tajiri, Kazuto; Tsuji, Kiichiro; Ishikawa, Toru; Ochi, Hironori; Hirooka, Masashi; Tsutsui, Akemi; Shibata, Hiroshi; Tada, Toshifumi; Toyoda, Hidenori; Nouso, Kazuhiro; Joko, Kouji; Hiasa, Yoichi; Michitaka, Kojiro

doi:10.1111/hepr.13243

Cited by 83 publications

(104 citation statements)

References 33 publications

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“…13,14 Thus, compared with sorafenib, lenvatinib could inhibit several additional cell signalings, including fibroblast growth factor (FGF) signaling. Similar to the results of the current study, the study by Hiraoka et al 17 also showed favorable treatment outcomes of lenvatinib for patients who had a history of TKI, supporting the results of the in vitro and vivo analyses. 15,16 Thus, lenvatinib might be effective for patients who previously failed to respond to sorafenib because lenvatinib could inhibit FGF signaling.…”

Section: Discussionsupporting

confidence: 91%

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting

et al. 2019

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Background and Aim Lenvatinib has been recently approved as a first‐line systematic therapy for patients with advanced hepatocellular carcinoma (HCC) based on the results of the phase 3 clinical trial REFLECT. This trial excluded patients with a history of systemic chemotherapy, bile duct invasion, and Child‐Pugh grade B. We aimed to investigate the efficacy and safety of lenvatinib for these patients and in the real‐world setting. Methods Among patients who were administered lenvatinib for advanced HCC between April and October 2018 in Hokkaido University Hospital and related hospitals, we evaluated those who were followed for more than 2 months and whose treatment response was evaluated via dynamic computed tomography at baseline and 2 months after treatment initiation. Meanwhile, patients were excluded if they had decompensated liver cirrhosis, were followed up less than 2 months, or were not evaluated at 2 months. Patients were also stratified according to compliance with the REFLECT inclusion criteria for further analysis. Results A total of 41 patients were included; more than 50% did not meet the REFLECT inclusion criteria. In total, 5 (12.2%), 20 (48.8%), 12 (29.3%), and 4 (9.3%) showed complete response, partial response, stable disease, and progressive disease, respectively. The objective response rate was 61.2%. The objective response rate and disease control rate were similar between patients who did and did not meet the REFLECT inclusion criteria. Moreover, the safety profile was also similar between the two patient groups. Conclusion Lenvatinib showed high early response rate and tolerability in patients with advanced HCC. Favorable outcomes were similarly observed in patients who did not meet the REFLECT inclusion criteria.

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Section: Discussionsupporting

confidence: 91%

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting

et al. 2019

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“…Physicians sometimes reduce lenvatinib doses due to lenvatinib‐related AEs . 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.…”

Section: Discussionmentioning

confidence: 51%

“…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 . These reports showed ORRs of 29.4–45.0% and DCRs of 60.0–93.0%.…”

Section: Discussionmentioning

confidence: 99%

“…In general, lenvatinib treatment is recommended only for patients with Child–Pugh A . 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 . 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.…”

Section: Methodsmentioning

confidence: 99%

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

Kuzuya

Ishigami

Ito

et al. 2019

Hepatology Research

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Aim We aimed to investigate the radiological antitumor response at 2 weeks after starting lenvatinib for patients with advanced hepatocellular carcinoma in real‐world practice. Methods This retrospective study enrolled 40 patients who received lenvatinib. Radiological antitumor response was evaluated according to the modified Response Evaluation Criteria in Solid Tumors. Results The objective response rate at 2 weeks and best overall response on confirmation of complete response, partial response (PR), and stable disease required (confirmed response) were 57.5% and 32.5%, respectively. Based on confirmed response, the overall survival rate was significantly longer in patients with an objective response rate than in those with stable disease or progressive disease after 12 months (73.2% and 54.2%, P = 0.0358). All 13 patients with an objective response rate on confirmed response were evaluated as PR at 2 weeks. The alpha‐fetoprotein ratio at 2 weeks was a significant factor associated with PR of response rate at 2 weeks. The median relative dose intensity from 2 to 6 weeks was significantly lower than that from 0 to 2 weeks (69.6% vs. 100%, P < 0.0001). Stratified by the antitumor response at 6 weeks considering the image evaluation at 2 weeks, the median relative dose intensity from 2 to 6 weeks was significantly lower in patients with progressive disease than in those with PR or stable disease (45.2% vs. 72.6%, P = 0.0482). Conclusions The radiological antitumor response at 2 weeks was favorable. Information on a favorable visible therapeutic response very early after lenvatinib initiation can help patients maintain their motivation for treatment, and allow physicians to continue treatment effectively and safely.

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“…To date, lenvatinib showed a higher ORR of 41.3% compared with sorafenib in a randomized phase II non‐inferiority trial, and it also showed the ORR of 37.5–40.7% assessed by modified Response Evaluation Criteria in Solid Tumors in clinical settings . Meanwhile, a relative higher ORR of 61.3% was reported in patients with intermediate‐stage HCC according to the Japanese subgroup analysis of a randomized phase III study .…”

Section: Discussionmentioning

confidence: 95%

Analyses of objective response rate, progression‐free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study

Hatanaka

Kakizaki

Nagashima

et al. 2019

Hepatology Research

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Aim The aim of this study was to investigate the predictive factors of objective response rate (ORR) and progression‐free survival (PFS), and the correlation of albumin‐bilirubin (ALBI) grade with decreased appetite and fatigue in hepatocellular carcinoma patients treated with lenvatinib. Methods From March 2018 to December 2018, a total of 94 patients was included in this retrospective multicenter study. Results The median age of all patients was 73 years (interquartile range 66–79.3 years), and approximately 78% patients were men. The ALBI grade was 1, 2, and 3 in 27 (28.7%), 64 (68.1%), and three patients (3.2%), respectively. The Barcelona Clinic Liver Cancer stage was early, intermediate, and advanced in one (1.1%), 22 (23.4%), and 71 patients (75.5%), respectively. Best radiological response was determined to complete response, partial response, stable disease, and progressive disease in 0 (0.0%), 24 (30.4%), 38 (48.1%), and 17 patients (21.5%), respectively, giving the ORR of 30.4%. The 3‐, 6‐, and 12‐month PFS was calculated to be 78.7% (95% CI 70.3–87.1%), 46.7% (95% CI 36.1–57.3%), and 17.4% (95% CI 6.6–28.2%). Multivariate analysis showed that the Barcelona Clinic Liver Cancer intermediate stage was shown to be the only significant factor affecting the ORR (odds ratio 3.78, 95% CI 1.14–12.5, P = 0.030) and PFS (hazard ratio 0.49, 95% CI 0.26–0.94, P = 0.030). The incidence of all grades of decreased appetite and fatigue was significantly less in patients with ALBI grade 1 compared with ALBI grade 2 + 3. Conclusions The Barcelona Clinic Liver Cancer intermediate stage was the predictive factor affecting the ORR and PFS, and ALBI grade was a good predictive factor affecting the incidence of fatigue and decreased appetite.

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Therapeutic potential of lenvatinib for unresectable hepatocellular carcinoma in clinical practice: Multicenter analysis

Abstract: Early therapeutic response to LEN was favorable. This new TKI could have therapeutic potential both in patients with and without past TKI treatments.

Cited by 83 publications

References 33 publications

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting

Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real‐world setting

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

Analyses of objective response rate, progression‐free survival, and adverse events in hepatocellular carcinoma patients treated with lenvatinib: A multicenter retrospective study

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