Lenvatinib for Hepatocellular Carcinoma: A Literature Review
Abstract
:1. Introduction
2. Therapeutic Response of Lenvatinib
2.1. The Ojective Response Rate of Lenvatinib
2.2. The Progression-Free Survival and Overall Survival
3. Adverse Events
3.1. The Fatigue, Appetite Loss and Treatment Discontinuation
3.2. The Hemorrhage Events
3.3. Hepatic Encephalopathy and Ascites
3.4. Thyroid Dysfunction
4. Lenvatinib for Patients with Barcelona Clinic Liver Cancer Intermediate Stage
4.1. Transcatheter Arterial Chemoembolization and Heterogeneity
4.2. Transcatheter Arterial Chemoembolization Refractoriness
4.3. Exceeding the up-to Seven Criteria, Transcatheter Arterial Chemoembolization Unsuitability and Upfront Systemic Therapies
5. Post-Progression Treatment after Lenvatinib
5.1. Changes in the Liver Function during Lenvatinib Treatment
5.2. The Frequency and Predictive Factors of Transition to Post-Progression Treatment
5.3. The Comparison of Sorafenib and Lenvatinib Treatment
6. Nutrition Assessment and Sarcopenia
6.1. Nutrition Assessment as a Prognostic Indicator
6.2. The Relationship between Sarcopenia and Overall Survival
7. Lenvatinib plus Pembrolizumab Therapy
8. Efficacy and Safety in Patients Excluded from the REFLECT Study
9. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Author/Ref. No. | Years | Country | No. of pts | ORR (%) | Median PFS (Months) | Median OS (Months) | Predictive Factors of ORR | Commentary | |
---|---|---|---|---|---|---|---|---|---|
mRECIST | RECIST ver.1.1 | ||||||||
Kudo M./[12] | 2018 | Global | 478 | 40.6 | 18.8 | 7.3 | 13.6 | NA | REFLECT trial |
Ueshima K./[17] | 2019 | Japan | 82 | 39.0 | NA | 7.6 | could not be reached | ALBI grade 1 | ALBI grade 1; ORR of 57.1%, median PFS of 18.9 months |
Hatanaka T./[18] | 2020 | Japan | 94 | 30.4 | NA | 5.4 | NA | BCLC intermediate stage | BCLC intermediate stage; ORR of 47.6%, median PFS 8.0 months |
Sasaki R./[19] | 2019 | Japan | 81 | 34.6 | 17.3 | NA | 11.6 | NA | The patients with the good ORR and those with high RDI had significantly good OS. |
Sho T./[20] | 2020 | Japan | 105 | 53.5 | NA | 9.8 | NA | NA | |
Ogushi K./[21] | 2020 | Japan | 181 | 30.4 | NA | NA | 369 (days) | CP-A, PS 0, RDI > 0.70 | CP-A; ORR of 36.5%. RDI > 0.70: ORR of 47.7%. CP-A and BCLC intermediate stage were the predictive factors affecting the OS. |
Maruta S./[22] | 2020 | Japan | 152 | 40.8 | 15.8 | 5.1 | 13.3 | NA | |
Ohki T./[23] | 2020 | Japan | 77 | 29.9 | NA | 5.6 | NA | CP-A, RDI > 70% at 30 days, AFP reduction | RDI > 70%; ORR of 45.2%, RDI ≤ 70%; ORR of 11.4%. The significant factors associated with the PFS were CP-5A, tumor size ≥ 40 mm among pretreatment factors. |
Hiraoka A./[24] | 2019 | Japan | 152 | 38.7 | NA | NA | could not be reached | NA | mALBI 2b or 3 was unfavorable predictive factor relevant to the OS. |
Wang D.X./[25] | 2020 | China | 54 | NA | 22.2 | 5.6 | could not be reached | could not be found in a multivariate analysis. | CP-A, BCLC intermediate stage and PVTT significantly affected the PFS. |
Cheon J./[26] | 2020 | Korea | 92 | NA | 14.1 | 4.3 | 7.1 | NA |
Author/Ref. No. | Years | No. of pts | Assessment | Time | Cut-off Value | Associated Factors | Therapeutic Response | Commentary |
---|---|---|---|---|---|---|---|---|
Sasaki R./[19] | 2019 | 81 | RDI | 8 weeks | 67% | BMI, PS, BCLC stage, platelet count, PT, albumin, initial dose | OS | Median OS could not be reached during the observation. |
Ogushi K./[21] | 2020 | 181 | RDI | 8 weeks | 70% | NA | ORR | Mean RDI gradually decreased from the start of lenvatinib to 2 months. |
Ohki T./[23] | 2020 | 77 | RDI | 30 days | 70% | NA | ORR, PFS | RDI > 70%; median PFS of 9.3 months |
Kirino S./[28] | 2020 | 60 | RDI | 4 weeks | 70% | Body weight, ALBI score, albumin, grade 3 or 4 adverse events | OS, time to discontinuation of treatment | Median OS could not be reached and median duration of lenvatinib was 9.5 months in patients with RDI > 70%. |
Ono A./[29] | 2020 | 41 | RDI | 4 weeks | 70% | Platelet count, albumin, AST, AFP-L3, DCP, ALBI score, TKI experience | PFS | RDI > 70%; median PFS of 6.7 months. RDI in 3–4 weeks significantly reduced compared to 1–2 weeks. |
Takahashi A./[30] | 2019 | 50 | RDI | 8 weeks | 75% | Child-Pugh class A, ALBI, EHS, initial dose | ORR, PFS | RDI > 75%; ORR of 68%, median PFS of 7.4 months |
Eso Y./[31] | 2019 | 49 | DBR, RDI | 60 days | DBR of 238.9, RDI of 66% | BSA, mALBI grade 1 + 2a, BTR | ORR, PFS | DBR was calculated as the delivered DI divided by BSA. |
Author/Ref. No. | Years | No. of pts | Frequency of Post-Progression Treatment | Frequency of Ramucirumab Treatment | Favorable Predictive Factors of Post-Progression Treatment |
---|---|---|---|---|---|
Hatanaka T./[35] | 2020 | 79 | 45.6% | 13.9% | ALBI grade 1, Child-Pugh score 5 |
Hiraoka A./[83] | 2020 | 73 | 43.8% | 20.0% | mALBI grade 1 + 2a |
Ando Y./[84] | 2020 | 53 | 50.9% | NA | mALBI grade 1 + 2a |
Author/Ref. No. | Years | No. of pts | Assessment | Cut-off Value |
---|---|---|---|---|
Tada T./[92] | 2020 | 237 | NLR | 4 |
Tada T./[93] | 2020 | 283 | PLR | 150 |
Shimose S./[95] | 2020 | 164 | CONUT score | 5 |
Hiraoka A./[101] | 2020 | 375 | PNI | 40 |
Uojima H./[103] | 2020 | 100 | SMI | 42 and 38 cm2/m2 in men and women, respectively |
Endo K./[104] | 2020 | 69 | grip strength | 26 kg and 18 kg in men and women, respectively |
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Hatanaka, T.; Naganuma, A.; Kakizaki, S. Lenvatinib for Hepatocellular Carcinoma: A Literature Review. Pharmaceuticals 2021, 14, 36. https://doi.org/10.3390/ph14010036
Hatanaka T, Naganuma A, Kakizaki S. Lenvatinib for Hepatocellular Carcinoma: A Literature Review. Pharmaceuticals. 2021; 14(1):36. https://doi.org/10.3390/ph14010036
Chicago/Turabian StyleHatanaka, Takeshi, Atsushi Naganuma, and Satoru Kakizaki. 2021. "Lenvatinib for Hepatocellular Carcinoma: A Literature Review" Pharmaceuticals 14, no. 1: 36. https://doi.org/10.3390/ph14010036