Lenvatinib For Hepatocellular Carcinoma Research Articles

Extracellular water to total body water ratio obtained by bioelectrical impedance analysis determines the dose intensity of lenvatinib for the treatment of patients with advanced hepatocellular carcinoma.

The aim of this study was to identify the factors that contribute to the maintenance of relative dose intensity (RDI) of lenvatinib in hepatocellular carcinoma (HCC) patients. Thirty-two patients with advanced HCC treated with lenvatinib were enrolled. We evaluated the relationship between maintenance of RDI and various clinical data, parameters obtained by body composition measurements with bioelectrical impedance analysis (BIA) and grip strength at the start of lenvatinib treatment. Multivariate analysis showed that only the extracellular water to total body water ratio (ECW/TBW) ≤0.400 at initiation of treatment was associated with RDI ≥50% (odds ratio, 6.94; 95% confidence interval [CI], 1.00-48.00; P=0.049). When the RDI was compared between ECW/TBW ≤0.400 group and ECW/TBW >0.400 group, the RDI was significantly higher in the ECW/TBW ≤0.400 group at each of 0-4W, 4-6W, and 6-8W points. The P value at each point was 0.003, 0.003, and 0.005, respectively. On the other hand, multivariate analysis showed that only the ECW/TBW ≤0.400 at initiation of treatment was associated with the extension of duration until reduction or withdrawal of lenvatinib (hazard ratio, 4.86; 95% CI, 1.52-15.50; P=0.007). The extracellular water to total body water ratio, a parameter of body composition measurement by BIA, was significantly associated with the maintenance of RDI and the duration until reduction or withdrawal of lenvatinib in HCC patients. In addition to standard predictors such as Child-Pugh score and modified albumin-bilirubin grade that have been used to date, ECW/TBW might be a new predictor of RDI in HCC patients treated with lenvatinib.

P-269 Lenvatinib in hepatocellular carcinoma: QoL surveys and radiological imaging markers predicting clinical outcome in patients with hepatocellular carcinoma treated with lenvatinib as first-line treatment (SULENVA-HCC)

Hepatocarcinoma (HCC) is the most frequent primary liver neoplasm. In most cases, the diagnosis of HCC occurs in a context of non-operability or metastatic disease for which systemic treatment is indicated. In Italy, two drugs are indicated and reimbursed as first-line setting for HCC: sorafenib and lenvatinib. Lenvatinib is a small multitarget molecule that selectively inhibits kinase activities of pathway-related proangiogenic and oncogenic receptors. The efficacy of lenvatinib has been demonstrated in the randomized phase III REFLECT clinical trial.

Real-world experience of pembrolizumab plus lenvatinib in unresectable hepatocellular carcinoma in Taiwan.

e16627 Background: Multi-kinase inhibitors and immune checkpoint inhibitors (ICIs) are treatment options of systemic therapy for unresectable hepatocellular carcinoma (HCC). Targeted therapy can potentially enhance T cell infiltration and activation, consequently, cooperate with ICIs to produce synergistic anti-tumor effects. The ongoing clinical trial shows promising data by combining pembrolizumab with lenvatinib for advanced HCC. The study tried to evaluate the treatment response and adverse events of pembrolizumab plus lenvatinib for HCC in real-world setting. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC in a tertiary medical center in Taiwan were prospectively enrolled. The status of HCC was either in advanced HCC or failed by prior locoregional treatment. The dosage of pembrolizumab was 100mg every 3 weeks. The starting dose of lenvatinib was 10mg per day then titrating to weight-based dose according to recommendation. Patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. The tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Till the end of Jan. 2020, 27 patients had received at least 2 cycles of pembrolizumab, and 17 had evaluable post-treatment images either by CT or MRI. There were 6 (22.2%) in BCLC B, and 21 (77.8%) in BCLC C. Of them, 17 (63%) were treated as the first-line systemic treatment, 8 as the second-line and 2 as the third line systemic treatment. Of the 17 cases with post-treatment image studies, there were 6 (35.3%) in partial response (PR), 7 (41.2%) in stable disease (SD), and 4 (23.5%) in progressive disease (PD) by RECIST v1.1; and 1 (5.8%) in complete response (CR), 9 (52.9%) in PR, 3 (17.6%) in SD and 4 (23.5%) in PD by mRECIST, respectively. The objective response rate (ORR) and disease control rate (DCR) by mRECIST were 58.7% and 76.5%, respectively. The most common TRAEs in any grade were hypertension 24 (88.4%), palmar-plantar syndrome 19 (70.4%), hypothyroidism 19(70.4%). The Grade 3/4 TRAEs were 3 (11.1%) with psoriasis-like skin reaction, 3 (11.1%) with hypertension and 2 (7.4%) with palmar-plantar syndrome. Conclusions: Pembrolizumab plus lenvatinib can produce excellent ORR and DCR with tolerable safety profiles. Such combination could be a promising strategy for unresectable HCC in the future.

Safety and efficacy of lenvatinib in HCC beyond second-line treatment.

e16592 Background: Until 2018 sorafenib was the only first-line systemic treatment option for advanced hepatocellular carcinoma (HCC). Ten years later a new agent, called lenvatinib, showed equal efficiency in comparison to sorafenib. Currently sorafenib and lenvatinib are options for first line treatment with regorafenib, cabozantinib and ramucirumab (if alpha fetoprotein > 400 ng / ml) as second-line treatment choices. The first published results from Imbrave150-trial shows promising effects regarding the combination of atezolizumab and bevacizumab for first line treatment in advanced HCC. This highlights the question for reasonable sequence therapies. Yet, it has so not been demonstrated, if lenvatinib is an option for a treatment line beyond the second. Methods: We identified 5 patients with advanced HCC from our hospital, who had been treated with local ablative procedures as well as at least three different systemic therapies with still excellent clinical performance status before receiving lenvatinib. Retrospective analysis was performed to examine clinical and radiologicresponse rates as well as side effects. Results: 3/5 patients achieved regression in at least third treatment lines. One patient showed stable disease, and only one of these five patients showed a mixed response. The toxicity profile was heterogeneous. One patient developed a mild hand-foot syndrome. Another one evolved hypertension. Developing of proteinuria led to stop treatment in one patient. One patient showed psychiatric disorder, which was possibly associated with lenvatinib. Response was independent of the underlying cause of HCC. Conclusions: Lenvatinib is a promising agent for treating advanced HCC in a later treatment line and revealed a tolerable toxicity profile.

Phase 2 study of lenvatinib in patients with advanced hepatocellular carcinoma

BackgroundLenvatinib is an oral inhibitor of vascular endothelial growth factor receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, RET, and KIT. This phase 2, single-arm, open-label multicenter study evaluated lenvatinib in advanced hepatocellular carcinoma (HCC).MethodsPatients with histologically/clinically confirmed advanced HCC who did not qualify for surgical resection or local therapies received lenvatinib at a dosage of 12 mg once daily (QD) in 28-day cycles. The primary efficacy endpoint was time to progression (TTP) per modified Response Evaluation Criteria in Solid Tumors v1.1; secondary efficacy endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS).ResultsBetween July 2010 and June 2011, 46 patients received lenvatinib at sites across Japan and Korea. The median TTP, as determined by independent radiological review, was 7.4 months [95 % confidence interval (CI): 5.5–9.4]. Seventeen patients (37 %) had partial response and 19 patients (41 %) had stable disease (ORR: 37 %; DCR: 78 %). Median OS was 18.7 months (95 % CI: 12.7–25.1). The most common any-grade adverse events (AEs) were hypertension (76 %), palmar-plantar erythrodysesthesia syndrome (65 %), decreased appetite (61 %), and proteinuria (61 %). Dose reductions and discontinuations due to AEs occurred in 34 (74 %) and 10 patients (22 %), respectively. Median body weight was lower in patients with an early (<30 days) dose withdrawal or reduction than in those without.ConclusionsLenvatinib 12-mg QD showed clinical activity and acceptable toxicity profiles in patients with advanced HCC, but early dose modification was necessary in patients with lower body weight. Further development of lenvatinib in HCC should consider dose modification by body weight.Trial registration IDwww.ClinicalTrials.gov NCT00946153.