Dataset Information

Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study.

ABSTRACT:

Background

Lenvatinib, a multikinase inhibitor, is an FDA-approved treatment for advanced hepatocellular carcinoma (HCC) in the first-line setting. Recent trial data have established atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab as preferred first-line treatment options for advanced HCC. The role of lenvatinib following progression on immunotherapy in patients with advanced HCC remains unclear.

Methods

We conducted a multicentric, retrospective analysis of patients with advanced HCC diagnosed between 2010 and 2021 at the Mayo Clinic in Minnesota, Arizona, and Florida who received immunotherapy followed by lenvatinib. Median overall survival and progression-free survival analyses were performed using the Kaplan-Meier method, and responses were determined using RECIST 1.1. Adverse events were determined using CTCAE v 4.0.

Results

We identified 53 patients with advanced HCC who received lenvatinib following progression on immunotherapy. Forty five (85%) patients had a Child Pugh class A at diagnosis, while 30 (58%) patients were still Child Pugh A at time of lenvatinib initiation. Lenvatinib was administered as a second-line treatment in 85% of the patients. The median PFS was 3.7 months (95% CI: 3.2-6.6), and the median OS from the time of lenvatinib initiation was 12.8 months (95% CI: 6.7-19.5). In patients with Child Pugh class A, the median OS and PFS was 14 and 5.2 months, respectively. Race, gender, and Child Pugh class was associated with OS on multivariate analysis.

Discussion

Our study, using real-world data, suggests that patients benefit from treatment with lenvatinib following progression on immunotherapy in advanced HCC. The optimal sequencing of therapy for patients with advanced HCC following progression on immunotherapy remains unknown, and these results need to be validated in a clinical trial.

SUBMITTER: Palmer ME

PROVIDER: S-EPMC10571707 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study.

Palmer Mathias E ME Gile Jennifer J JJ Storandt Michael H MH Jin Zhaohui Z Zemla Tyler J TJ Tran Nguyen H NH Mahipal Amit A

Cancers 20231006 19

<h4>Background</h4>Lenvatinib, a multikinase inhibitor, is an FDA-approved treatment for advanced hepatocellular carcinoma (HCC) in the first-line setting. Recent trial data have established atezolizumab plus bevacizumab as well as tremelimumab plus durvalumab as preferred first-line treatment options for advanced HCC. The role of lenvatinib following progression on immunotherapy in patients with advanced HCC remains unclear.<h4>Methods</h4>We conducted a multicentric, retrospective analysis of ...[more]

PMID: 37835561

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Project description:BackgroundGiven the significant advancements in the management of hepatocellular carcinoma (HCC) and the emergence of novel treatment approaches, establishing reliable predictors has become crucial for optimizing patient selection and therapeutic sequencing in HCC. In this study, we aimed to investigate the prognostic factors and treatment efficacy associated with lenvatinib-based therapy.MethodsWe retrospectively enrolled 53 patients receiving lenvatinib monotherapy, and 19 patients receiving lenvatinib plus immune checkpoint inhibitor combination therapy as their first-line systemic treatment for unresectable HCC at a single medical center. We employed univariate and multivariate Cox regression analyses to ascertain the factors influencing survival in these cohorts.ResultsFor lenvatinib monotherapy and the combination therapy, the objective response rates were 30.2% and 63.2%, respectively (P=0.03); the median progression-free survival (PFS) durations were 7 months [95% confidence interval (CI): 4.5-9.5] and 12 months (95% CI: 6.4-17.6), respectively (P=0.74); and the median overall survival (OS) was not reached in either group (P=0.93). Although patients receiving the combination therapy had a greater treatment response, no significant survival differences were observed between the lenvatinib monotherapy and combination therapy subgroups, even after inverse probability of treatment weighting (IPTW). Patients who received lenvatinib monotherapy could be stratified based on a combination of albumin-bilirubin (ALBI) grade (either grade 1 or 2a) and a neutrophil-lymphocyte ratio (NLR) of ≤5.8. Compared to the other subgroups combined, those who met both of these criteria exhibited PFS with a hazard ratio (HR) of 0.382 (95% CI: 0.168-0.871; P=0.02), corresponding to 11 and 5 months, respectively; and an OS (HR: 0.198, 95% CI: 0.043-0.920; P=0.04) of not reached versus 12 months, respectively, according to multivariate Cox regression analysis.ConclusionsIn our study cohort, there were no statistically significant differences observed in the survival rates between patients treated with lenvatinib monotherapy and those treated with a combination of lenvatinib and immunotherapy. The incorporation of ALBI grade and NLR facilitates the stratification of survival outcomes in patients with unresectable HCC undergoing lenvatinib monotherapy.

Project description:Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide and accounts for 90% of all primary liver cancers. Chronic inflammation is the hallmark across most prevalent etiologies among which HBV is the leading cause worldwide (33%), followed by alcohol (30%), HCV (21%), other factors like non-alcoholic steatohepatitis linked to insulin resistance/metabolic syndrome, and obesity associated inflammation (16%). Deregulation of the tightly controlled immunological network leads to liver disease, including chronic infection, autoimmunity, and tumor development. While inflammation drives oncogenesis in the liver, HCC also recruits ICOS+ FOXP3+ Tregs and MDSCs and upregulates immune checkpoints to induce a state of immunosuppression in the tumor microenvironment. As such, research is focused on targeting and modulating the immune system to treat HCC. The Checkmate 040 and Keynote 224 studies established the role of immunotherapy in the treatment of patients with HCC. In Phase I and II trials, nivolumab and pembrolizumab demonstrated durable response rates of 15-20% and were subsequently approved as second-line agents after sorafenib. Due to the success of the IMbrave 150 and HIMALAYA trials, which examined the combination of atezolizumab/bevacizumab and tremelimumab/durvalumab, respectively, the FDA approved these regimens as first-time treatment options for patients with advanced HCC. The encouraging results of immunotherapy in the management of HCC has led researchers to evaluate if combination with locoregional therapies may result in a synergistic effect. Real-world studies represent an invaluable tool to assess and verify the applicability of clinical trials in the bedside setting with a more varied patient population. We herein review current real-life use of ICIs in the management of HCC and highlight some of the ongoing clinical trials that are expected to change current recommended first-line treatment in the near future.

Project description:BackgroundLenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trials. This study was to compare the effectiveness and safety of lenvatinib and sorafenib in the real world.MethodsWe retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib treatment between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between the two groups.ResultsA total of 210 patients (Male/Female: 150/60, mean age: 65.8 years) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3 vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence interval: 0.3-0.79, p=0.004) after adjustments of albumin-bilirubin grade and alpha-fetoprotein level; however, different agents using lenvatinib or sorafenib did not contribute to OS, whether in univariate or multivariate analysis. Patients who failed lenvatinib had a lower proportion of having sequential systemic therapies compared with the Sorafenib group (36.2 vs 47.8%, p=0.02). The most frequently used sequential therapy following lenvatinib and sorafenib was chemotherapy (n=9, 42.8%) and regorafenib (n=33, 50.8%), respectively.ConclusionsIn clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC, while reducing the risk of progression disease compared with sorafenib. Additionally, lack of approved post-lenvatinib systemic therapies is a serious issue in the real world.

Project description:BackgroundLenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria.MethodsA retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed.ResultsPatients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC.ConclusionOverall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

Dataset Information

Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study.

Background

Methods

Results

Discussion

Publications

Outcomes of Patients with Advanced Hepatocellular Carcinoma Receiving Lenvatinib following Immunotherapy: A Real World Evidence Study.

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