Understanding Lenvatinib in the Treatment of Advanced Hepatocellular Carcinoma (HCC)
Lenvatinib, an oral multikinase inhibitor, has emerged as a cornerstone in the management of this challenging malignancy. This webpage delves into the nuances of Lenvatinib therapy, offering insights into its therapeutic efficacy, safety profile, and the evolving landscape of treatment strategies.
Our discussion encompasses a range of topics, from the drug’s impact on survival rates and progression-free survival to its role in managing different stages of liver cancer, particularly the Barcelona Clinic Liver Cancer (BCLC) intermediate stage. We explore the adverse events associated with Lenvatinib, emphasizing the importance of managing these events to ensure treatment continuity and patient well-being.
Additionally, we address the critical aspects of post-progression treatment strategies, the significance of nutrition assessment and sarcopenia in patient outcomes, and the promising potential of combining Lenvatinib with Pembrolizumab. Our goal is to provide a comprehensive overview that aids patients, caregivers, and healthcare professionals in understanding the multifaceted role of Lenvatinib in treating advanced HCC.
| Category | Subcategory | Details | Statistics | Other Keypoints |
|---|---|---|---|---|
| 1. Therapeutic Response | Objective Response Rate (ORR) | Real-world studies: ORR range by mRECIST and RECIST ver.1.1 | 29.9–53.5% (mRECIST), 14–25% (RECIST ver.1.1) | High ORR was found in patients with albumin-bilirubin (ALBI) grade 1 at baseline, good PS, Child-Pugh class A, and Child-Pugh score 5 (CP-5A) |
| Progression-Free Survival (PFS) | Median PFS in phase 3 and retrospective studies | 4.3–9.8 months (Retrospective), 7.3 months (Phase 3) | The PFS in patients with extrahepatic spread, incidence of thyroid dysfunction and appetite loss was shorter. | |
| Overall Survival (OS) | Median OS in phase 3 and retrospective studies | 7.1–13.3 months (Retrospective), 13.6 months (Phase 3) | modified ALBI (mALBI) grade 2b or 3, Child-Pugh class B, BCLC advanced stage, and elevated C-reactive protein were found to be significant unfavourable factors in different studies. | |
| 2. Adverse Events | Common Events | Fatigue, appetite loss, HFSR, diarrhoea, hypertension (median onset after 4 days), hypothyroidism, proteinuria | Discontinuation rate: 8.6–43.5% Hypothyroidism: 12-24% | Appetite loss was strongly correlated with the therapeutic effect. |
| Hemorrhage Events | Intracranial, intraperitoneal, intratumoral haemorrhages | 2.6% in Western countries and 10–26% in Asian countries | ||
| Hepatic Encephalopathy & Ascites | Risk factors: elevated ammonia, portosystemic shunt presence | approximately 29% patients | Child-Pugh score 6 and a low platelet count (<12 × 104/μL) were significant risk factors | |
| 3. Treatment Strategy for BCLC Intermediate Stage | TACE Refractoriness & Unsuitability | Indications for switching from TACE to systemic therapy | Median PFS in TACE-refractory patients that were treated with lenvatinib, sorafenib, and TACE was 5.8, 3.2, and 2.4 months, respectively | A. AASLD Consensus on TACE Application: TACE is considered the best approach for patients who have a low tumor burden and nodules that are accessible super-selectively. Recommendation for Upfront Systemic Therapy: |
| Upfront Systemic Therapies (patients who exceed the up-to seven criteria, indicating a higher tumor burden or complexity.) | Up-to-seven criteria, TACE unsuitability | No specific statistics provided | A. TACE Unsuitability Criteria (APPLE Consensus Statement): 1. Unlikely to Respond to TACE: This includes patients with confluent multinodular type, massive or infiltrative type, simple nodular type with extranodular growth, poorly differentiated type, intrahepatic multiple disseminated nodules, or sarcomatous changes after TACE. 2. Likely to Develop TACE Failure/Refractoriness: This is indicated for patients exceeding the up-to seven criteria. 3. Risk of Progression to Child-Pugh B or C Post-TACE: Patients are at risk if they exceed the up-to seven criteria and have a modified ALBI (mALBI) grade 2b. |
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| 4. Post-Progression Treatment | Liver Function Changes | ALBI score, parameters associated with liver function during treatment | No specific statistics provided | Male sex, ALBI grade 1, CP-5A, and BCLC early or intermediate stage were significant favourable factors |
| 5. Nutrition Assessment & Sarcopenia | Nutrition Assessment as Prognostic Indicator | Various nutrition assessment tools | No specific statistics provided | Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, CONUT score (overall survival were significantly longer in patients with low CONUT score <5), and PNI. Strong correlation with ALBI score. |
| Sarcopenia: Defined by reduced muscle mass and strength. | Impact of sarcopenia on OS and treatment efficacy | No specific statistics provided | High skeletal muscle mass (SMI) associated with better OS. Sarcopenia might impact lenvatinib treatment efficacy. | |
| 6. Combination Therapy | Lenvatinib plus Pembrolizumab | ORR, PFS, OS in phase 1b study | ORR: 46% (mRECIST), 36% (RECIST ver.1.1), Median PFS: 9.3 months, OS: 22.0 months |