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

Sho, Takuya; Suda, Goki; Ogawa, Koji; Kimura, Megumi; Shimazaki, Tomoe; Maehara, Osamu; Shigesawa, Taku; Suzuki, Kazuharu; Nakamura, Akihisa; Ohara, Masatsugu; Umemura, Machiko; Kawagishi, Naoki; Natsuizaka, Mitsuteru; Nakai, Masato; Morikawa, Kenichi; Furuya, Ken; Baba, Masaru; Yamamoto, Yoshiya; Kobayashi, Tomoe; Meguro, Takeshi; Saga, Akiyoshi; Miyagishima, Takuto; Yokoo, Hideki; Kamiyama, Toshiya; Taketomi, Akinobu; Sakamoto, Naoya

doi:10.1002/jgh3.12209

Cited by 37 publications

(47 citation statements)

References 23 publications

(13 reference statements)

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“…However, the current study found that patients who fulfilled the REFLECT eligibility criteria showed better DCR and OS than those of patients who did not fulfill the REFLECT eligibility criteria (DCR: 85.4 vs. 68.3%, p value 0.045, median OS duration: 13.9 months [8.1–19.7] vs. 8.7 months [7.6–9.8]), which confronts the result from the recent Japanese study of 41 patients with unresectable HCC [19]. This is due to the difference in detail components of patients who did not fulfill the REFLECT eligibility criteria.…”

Section: Discussionmentioning

confidence: 52%

Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Goh

Kim

et al. 2021

Liver Cancer

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Background: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. Methods: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. Results: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. Conclusion: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

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Section: Discussionmentioning

confidence: 52%

Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Goh

Kim

et al. 2021

Liver Cancer

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“…The results of the REFLECT trial and clinical data have widened the therapeutic options for patients with unresectable HCC. 7,15 Currently, patients with unresectable HCC may be treated with either sorafenib or lenvatinib in the first line. However, to date, criteria for their selection based on patients' characteristics have not been established.…”

Section: Discussionmentioning

confidence: 99%

Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

et al. 2020

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Background: Sorafenib and lenvatinib are first-line systemic therapies for unresectable hepatocellular carcinoma (HCC). However, the criteria for their selection remain unclear. Methods: We identified patients with unresectable HCC who were treated with sorafenib or lenvatinib between August 2009 and January 2019 at the Hokkaido University Hospital. Patients who continued treatment for >2 months, underwent evaluation by computed tomography every 2-3 months, and had complete clinical data were included. Responders were patients with objective response (OR) for lenvatinib and patients with stable disease (SD) exceeding 6 months (long-SD) or OR for sorafenib. The predictive factors for treatment response, including fibroblast growth factor (FGF)19 and 21, angiopoietin 2 (ANG2), hepatocyte growth factor, and vascular endothelial growth factor, were evaluated. Results: Overall, 27 and 29 patients treated with lenvatinib and sorafenib, respectively, were included. The responders for lenvatinib and sorafenib were 63% (17/27) and 38% (11/29), respectively. No significant predictive factors for treatment response were identified in patients treated with sorafenib. However, baseline serum FGF19 and ANG2 levels were significantly associated with treatment response to lenvatinib. All (9/9) patients with low baseline ANG2 and FGF19 levels who received lenvatinib achieved OR. Conversely, the OR was low (13%; 1/9) in patients with high baseline ANG2 and FGF19 levels. Responder rate was 40% (2/5) in patients with high baseline ANG2 and FGF19 levels who received sorafenib. Conclusion: This study is, to our knowledge, the first to demonstrate that baseline ANG2 and FGF19 levels may aid in selecting optimal systemic therapy for patients with unresectable HCC.

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“…Consistent with our results, it has been reported that portal hypertension-induced slow blood flow increases ANG2 expression [ 27 , 28 ]. We and other groups have shown that, in patients with advanced HCC, high serum ANG2 levels were sometimes observed [ 29 , 16 ]. Additionally, several recent studies have revealed that high ANG2 expression could predict pathological angiogenesis in nonalcoholic steatohepatitis, occurrence and recurrence of HCC after direct-acting antiviral therapy, mortality, and deterioration of kidney function in decompensated cirrhosis [ 28 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…Lenvatinib, which targets VEGFR1-3, fibroblast growth factor receptors 1-4, plateletderived growth factor receptor-α, c-Kit, and rearranged during transfection proto-oncogene [11,12], demonstrated non-inferiority to sorafenib in terms of OS in unresectable HCC [8]. The efficacy and safety of lenvatinib in patients with unresectable HCC have been demonstrated in a real-world setting [13][14][15][16][17]. However, some patients experienced deterioration of the liver functional reserve during lenvatinib treatment for HCC.…”

Section: Introductionmentioning

confidence: 99%

Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma

et al. 2021

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A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.

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

Cited by 37 publications

References 23 publications

Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Efficacy and Safety of Lenvatinib Therapy for Unresectable Hepatocellular Carcinoma in a Real-World Practice in Korea

Baseline angiopoietin‐2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma

Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma

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