scholarly journals Lenvatinib as First-line Treatment of Hepatocellular Carcinoma in Patients with Impaired Liver Function in Advanced Liver Cirrhosis: Real World Data and Experience of a Tertiary Hepatobiliary Center

2021 ◽  
Author(s):  
Lidia-Sabina Cosma ◽  
Kilian Weigand ◽  
Martina Müller-Schilling ◽  
Arne Kandulski
Keyword(s):  
Liver Function ◽  
Survival Benefit ◽  
Line Treatment ◽  
First Line ◽  
Impaired Liver Function ◽  
Class A ◽  
Impaired Liver ◽  
Class B ◽  
Pugh Class ◽  
First Line Treatment

Background and Aims: Lenvatinib is a multikinase inhibitor approved for systemic first line treatment of hepatocellular cancer (HCC) in patients with compensated liver cirrhosis (LC) and unaltered liver function. We aimed to evaluate the efficiency and tolerability of lenvatinib in patients with HCC in a real world setting, also including patients with advanced LC and impaired liver function. Methods: Retrospectively, 35 patients with HCC BCLC stages B, C and D were screened. After drop-out and exclusion of patients not receiving active treatment for > 2 weeks, 28 patients (27 male; median age 64.7) with advanced HCC and LC were included in the analysis. Results: Fourteen patients (male, median age 62.7) treated had Child-Pugh class B LC, while the other 12 patients had a good liver function Child-Pugh class A (male, median age 68.8). Two patients had advanced Child-Pugh class C LC. The patients received an escalating dosing scheme of lenvatinib up to 12 mg/d. The tolerability of lenvatinib was similar in most of the patients, with no significant difference between the subgroups. Median survival was better in patients with Child-Pugh A LC (p=0.003). More than 60% of the patients with Child-Pugh A were still on treatment at the time of data analysis with a median follow-up of 274 ± 117.5 days compared with 153 days (95%CI: 88.3 – 217.7) in patients with Child-Pugh B and 30 days in Child-Pugh C. The survival benefit correlated significantly with less impaired liver function (p=0.003). Conclusion: Tolerability and toxicity of lenvatinib are similar in patients withChild-Pugh class A and class B LC, but patients with less impaired liver function have a better survival benefit.

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Oncology ◽  
2020 ◽  
Vol 98 (11) ◽  
pp. 787-797 ◽  
Author(s):  
Yuwa Ando ◽  
Tomokazu Kawaoka ◽  
Yosuke Suehiro ◽  
Kenji Yamaoka ◽  
Yumi Kosaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Multivariate Analysis ◽  
Liver Function ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Class A ◽  
Line Therapy ◽  
Pugh Class ◽  
Ecog Ps

<b><i>Background:</i></b> Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. <b><i>Methods:</i></b> Patients (<i>n</i> = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. <b><i>Results:</i></b> One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: <i>n</i> = 26; ramucirumab: <i>n</i> = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465–18.31, <i>p</i> = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (&#x3c;400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099–0.886, <i>p</i> = 0.003), a relative tumor volume &#x3c;50% at the time of progression (HR 0.204, 95% CI 0.07–0.592, <i>p</i> = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12–0.746, <i>p</i> = 0.01) were significant prognostic factors. <b><i>Conclusion:</i></b> Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

scholarly journals Cost-effectiveness analysis of cetuximab combined with chemotherapy as a first-line treatment for patients with RAS wild-type metastatic colorectal cancer based on the TAILOR trial

BMJ Open ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. e030738 ◽  
Author(s):  
Huijuan Wang ◽  
Lingfei Huang ◽  
Peng Gao ◽  
Zhengyi Zhu ◽  
Weifeng Ye ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cost Effectiveness ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Cost Effective ◽  
Phase Iii ◽  
Line Treatment ◽  
Wild Type ◽  
First Line ◽  
First Line Treatment

ObjectivesCetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX-4) is superior to FOLFOX-4 alone as a first-line treatment for patients with metastatic colorectal cancer with RAS wild-type (RAS wt mCRC), with significantly improved survival benefit by TAILOR, an open-label, randomised, multicentre, phase III trial. Nevertheless, the cost-effectiveness of these two regimens remains uncertain. The following study aims to determine whether cetuximab combined with FOLFOX-4 is a cost-effective regimen for patients with specific RAS wt mCRC in China.DesignA cost-effectiveness model combined decision tree and Markov model was built to simulate pateints with RAS wt mCRC based on health states of dead, progressive and stable. The health outcomes from the TAILOR trial and utilities from published data were used respectively. Costs were calculated with reference to the Chinese societal perspective. The robustness of the results was evaluated by univariate and probabilistic sensitivity analyses.ParticipantsThe included patients were newly diagnosed Chinese patients with fully RAS wt mCRC.InterventionsFirst-line treatment with either cetuximab plus FOLFOX-4 or FOLFOX-4.Main outcome measuresThe primary outcomes are costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsBaseline analysis disclosed that the QALYs was increased by 0.383 caused by additional cetuximab, while an increase of US$62 947 was observed in relation to FOLFOX-4 chemotherapy. The ICER was US$164 044 per QALY, which exceeded the willingness-to-pay threshold of US$28 106 per QALY.ConclusionsDespite the survival benefit, cetuximab combined with FOLFOX-4 is not a cost-effective treatment for the first-line regime of patients with RAS wt mCRC in China.Trial registration numberTAILOR trial (NCT01228734); Post-results.

Effect of the addition of bevacizumab to first-line FOLFOX on efficacy, including response rate, progression-free survival, and overall survival, in patients with metastatic colorectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 588-588
Author(s):  
M. Suenaga ◽  
N. Mizunuma ◽  
S. Matsusaka ◽  
E. Shinozaki ◽  
M. Ogura ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Metastatic Colorectal Cancer ◽  
Survival Benefit ◽  
Response Rate ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
First Line Treatment

588 Background: Bevacizumab (BV) is a recombinant, humanized monoclonal antibody against vascular endothelial growth factor. Used in combination with chemotherapy, BV has been shown to improve survival in both first- and second-line treatment for metastatic colorectal cancer (mCRC). However, it was reported that addition of BV to FOLFOX conferred only little survival benefit (Saltz et al. JCO2008). The aim of this study was to assess the efficacy of addition of BV to FOLFOX in first-line treatment for patients with mCRC. Methods: Bevacizumab was approved for mCRC in July 2007 in Japan. This study was conducted at a single institution and comprised 217 consecutive patients receiving first-line treatment for mCRC between 2005 and 2009. The primary objective was to compare survival benefit in patients treated with FOLFOX4 (FF) between 2005 and 2007 with that in patients receiving FOLFOX4+BV 5 mg/kg (FF+BV) between 2007 and 2009. Results: Total number of patients in the FF and FF+BV groups was 132 and 85, respectively. Characteristics of patients were as follows (FF vs. FF+B): median age, 62 yrs (range 28-76 yrs) vs. 60 yrs (range16-74 yrs); ECOG PS0, 98.8% vs. 81.8%; and median follow-up time, 20.8 months vs. 24.4 months. Median progression-free survival (PFS) in the FF and FF+BV groups was 10 months (95% CI, 8.7-11.3) and 17 months (95% CI, 10.2-14.1), while median overall survival (OS) was 21 months (95% CI, 17.9-24.1) and not reached, respectively. Response rate was 46% (95% CI, 37- 54) in FF, and 62% (95% CI, 51-73) in FF+BV. Addition of BV to FOLFOX4 significantly improved PFS (p=0.002) and OS (p<0.001). Conclusions: The additive effect of BV for first-line FOLFOX was reconfirmed. These data indicate potential survival benefits from the addition of BV to FOLFOX in first-line treatment of mCRC. In addition, PFS may be a sensitive indicator of outcome prior to post-treatment. No significant financial relationships to disclose.

scholarly journals Development of a Model to Predict Liver Decompensation prior to Transarterial Chemoembolization Refractoriness in Patients with Intermediate-Stage Hepatocellular Carcinoma

2021 ◽  
pp. 1-9
Author(s):  
Joel Ferreira-Silva ◽  
Pedro Costa-Moreira ◽  
Helder Cardoso ◽  
Rodrigo Liberal ◽  
Pedro Pereira ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transarterial Chemoembolization ◽  
Objective Response ◽  
Intermediate Stage ◽  
Line Treatment ◽  
First Line ◽  
Hepatic Reserve ◽  
Liver Decompensation ◽  
Pugh Class ◽  
First Line Treatment

<b><i>Introduction:</i></b> Transarterial chemoembolization (TACE) is the first-line treatment for patients with intermediate-stage hepatocellular carcinoma (HCC). For patients without an adequate response, current finding suggests that treatment with molecular target agents, approved for advanced stage, might present benefits. However, this requires a preserved liver function. This study aims to evaluate possible predictors of early deterioration of hepatic reserve, prior to TACE refractoriness, in a cohort of patients treated with TACE. <b><i>Methods:</i></b> Retrospective analysis of 99 patients with<b><i></i></b>Child-Pugh class A and intermediate-stage HCC who underwent TACE as the first-line treatment. All patients were submitted to a biochemical and medical evaluation prior to initial TACE and every month afterward. Response to initial TACE was evaluated at 1 month. The time to Child-Pugh class deterioration before TACE refractoriness was assessed. <b><i>Results:</i></b> Ninety-nine patients were included. Objective response rate (ORR) to initial TACE was assessed as present in 59 (63.4%) and as absent in 34 (36.6%) patients. Liver decompensated before TACE refractoriness in 51 (51.5%) patients, and the median time to liver decompensation was 14 (IQR 8–20) months after first TACE. In multivariate analysis, beyond up-to-7 criteria (HR 2.4, <i>p</i> = 0.031), albumin &#x3c;35 mg/dL (HR 3.5, <i>p</i> &#x3c; 0.001) and absence of ORR (HR 2.4, <i>p</i> = 0.020) were associated with decreased overall survival free of liver decompensation. Moreover, beyond up-to-7 criteria, albumin &#x3c;35 mg/dL and absence of ORR associated negatively with 6-month survival free of liver decompensation. Our model created using those variables was able to predict liver decompensation at 6 months with an AUROC of 0.701 (<i>p</i> = 0.02). <b><i>Conclusions:</i></b> The absence of ORR after initial TACE, beyond up-to-7 criteria and albumin &#x3c;35 mg/dL, was a predictive factor for early liver decompensation before TACE refractoriness in our population. Such patients might benefit from treatment escalation to systemic therapy, in monotherapy or in combination with TACE.

Propensity Score Matching Analysis Comparing Azathioprine Plus Prednisone Vs Prednisone Alone Regimens As First-Line Treatment in Chronic Graft-Versus-Host Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3126-3126
Author(s):  
Jieun Uhm ◽  
Elizabeth Shin ◽  
Fotios V. Michelis ◽  
Auro Viswabandya ◽  
Jeffrey H. Lipton ◽  
...  
Keyword(s):  
Propensity Score ◽  
Survival Benefit ◽  
Research Funding ◽  
Performance Status ◽  
Case Control ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Steroid Sparing ◽  
First Line Treatment

Abstract Background: Azathioprine (AZA) has been used as a steroid sparing agent in allogeneic BMT program at the Princess Margaret Cancer Centre, Toronto, Canada for last two decades especially for cGVHD treatment. A previous clinical trial (Sullivan, Blood 1998) compared prednisone (PRD) alone vs PRD plus AZA for the treatment of extensive chronic GVHD (cGVHD) suggesting that PRD alone showed a better survival than PRD+AZA. However, the NIH consensus criteria (NCC, 2005) for cGVHD and new statistic endpoint to evaluate efficacy of cGVHD, failure free survival (FFS), have been recently introduced and increasingly used. Therefore, we conducted retrospective study attempted to evaluate the efficacy of PRD+AZA regimen compared to PRD alone regimen with respect to failure free survival (FFS) as well as overall survival (OS), non-relapse mortality (NRM)and relapse incidence. In order to adjust for the risk factors which affect the choice of treatment between different treatment options, propensity score matching (PSM) analysis was adopted in the present study. Methods: The patients diagnosed with late onset acute GVHD was excluded. A total of 240 patients were included in the analysis, transplanted at the Princess Margret Cancer Center between 2009 and 2013, diagnosed with cGVHD by NCC, and treated with PRD+AZA (n=98) or PRD alone (n=142) as first line treatment. Failure free survival (FFS), OS, NRM and relapse were compared between the 2 groups. A case-control study was performed with well-balanced pairs of PRD+AZA vs PRD patients. For the PSM analysis, propensity score (PS) was calculated. Clinical variables included in PS calculation were global score (GS) by NCC, subtype of cGVHD (classical vs overlapping), age, gender, duration from HCT to cGVHD initial treatment, performance status (PS), progressive type onset (PTO) of cGVHD, thrombocytopenia (TP) and each organ involvement of cGVHD per skin, gastrointestinal tract, liver, lung and musculoskeletal system. A total of 74 case-control pairs were selected within 0.1 of a difference in propensity score. RESULTS: With a follow-up of 43. 6 months, the 2-year FFS, OS, NRM and relapse incidence was 24.7 %, 75.6 %, 16.6% and 7.7%, respectively. The median FFS was 7.9 months (95% CI, 6.1-9.6 months). PRD+AZA group showed a longer FFS duration compared to PRD group (13.2 vs 5.6 months, p<0.001). In addition, PRD+AZA showed a lower NRM rate than PRD group (10.8% vs 20.6% at 2 years, p=0.008). A trend of lower relapse risk was noted in PRD+AZA over PRD group (2.6%vs 11.0% at 2 years, p=0.074). Within the overall population, imbalanced demographic and disease characteristics were observed between the 2 groups, including longer duration from HCT to cGVHD initial treatment (p<0.001), fewer patients with severe GS by NCC (p<0.001), fewer patients with PTO (p=0.002), fewer with TP (p=0.008) and better performance status (p=0.008) in the PRD+AZA group. After PSM procedure, all clinical variables became well balanced between the 2 groups. The PSM analysis successfully confirmed our previous observation of superior outcomes in PRD+AZA group to those in PRD group. The median FFS duration was significantly longer in PRD+AZA (17.6 months) compared to PRD group (7.4 months, p<0.001). There was a trend of survival benefit in favor of PRD+AZA group (87.4% vs 78.2% at 2 years; p=0.074). There was no significant difference between 2 groups in NRM (p=0.289) and relapse rate at 2 years (p=0.187). Confined to the same NCC GS group, there was a trend of a longer FFS in PRD+AZA compared to PRD group. In the group with moderate grade of cGVHD, a longer FFS duration was noted in PRD+AZA than in PRD alone ( 11.1 vs 7.4 months, p=0.001). Compared to PRD group, PRD+AZA group showed a higher success rate of PRD tapering below 0.5mg/Kg/day by first 6 months (90.5% in PRD+AZA vs 75.8% in PRD group, p=0.018). Conclusion: The present study suggested that 1) addition of AZA in the PRD based regimen for cGVHD treatment could improve FFS in patients with cGVHD requiring systemic immunosuppression, and that 2) AZA did not increase the risk of relapse and may have a survival benefit with rapid reduction of corticosteroid or delay of switch to second line treatment. Thus AZA should be considered as a therapeutic option for steroid sparing agent in frontline cGVHD treatment, PRD based. Disclosures Kim: Bristol-Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding.

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