FRI-499-Efficacy and hepatic safety of nivolumab treatment in patients with Child-Pugh B disease and advanced hepatocellular carcinoma in CheckMate 040

Sangro, Bruno; Matilla, Ana; Santoro, Armando; Melero, Ignacio; Gracián, Antonio Cubillo; Acosta, Mirelis; Choo, Su-Pin; El-Khoureiry, Anthony; Kuromatsu, Ryoko; El‐Rayes, Bassel F.; Numata, Kazushi; Itoh, Yoshito; Costanzo, Francesco Di; Crysler, Oxana; Reig, María; Shen, Yun; Neely, Jaclyn; Cruz, Christine Marie Dela; Baccan, Carlos; Kudo, Masatoshi

doi:10.1016/s0618-8278(19)31234-4

Cited by 5 publications

(3 citation statements)

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“…In CheckMate-040, patients with best overall response of CR/PR maintained a stable ALBI score and grade during treatment, but the majority of patients with SD/PD had a worsening of both ALBI scores and grade based on maximum post-baseline value compared with baseline. 46 Because of the lack of a control arm in the CheckMate-040 study, 46 it is difficult to determine whether these differences were influenced by the enrolled patient population and disease setting, or possibly by the frequency of laboratory measurements and radiographic assessments. Changes in ALBI score/grade during study treatment with an immune checkpoint inhibitor have not been reported in a randomised controlled trial.…”

Section: Discussionmentioning

confidence: 99%

Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

et al. 2021

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Background & Aims The albumin–bilirubin (ALBI) grade/score is derived from a validated nomogram to objectively assess prognosis and liver function in patients with hepatocellular carcinoma (HCC). In this post hoc analysis, we assessed prognosis in terms of survival by baseline ALBI grade and monitored liver function during treatment with ramucirumab or placebo using the ALBI score in patients with advanced HCC. Methods Patients with advanced HCC, Child-Pugh class A with prior sorafenib treatment were randomised in REACH trials to receive ramucirumab 8 mg/kg or placebo every 2 weeks. Data were analysed by trial and as a meta-analysis of individual patient-level data (pooled population) from REACH (alpha-fetoprotein ≥400 ng/ml) and REACH-2. Patients from REACH with Child-Pugh class B were analysed as a separate cohort. The ALBI grades and scores were calculated at baseline and before each treatment cycle. Results Baseline characteristics by ALBI grade were balanced between treatment arms among patients in the pooled population (ALBI-1, n = 231; ALBI-2, n = 296; ALBI-3, n = 7). Baseline ALBI grade was prognostic for overall survival (OS; ALBI grade 2 vs. 1; hazard ratio [HR]: 1.38 [1.13–1.69]), after adjusting for other significant prognostic factors. Mean ALBI scores remained stable in both treatment arms compared with baseline and were unaffected by baseline ALBI grade, macrovascular invasion, tumour response, geographical region, or prior locoregional therapy. Baseline ALBI grades 2 and 3 were associated with increased incidence of liver-specific adverse events and discontinuation rates in both treatments. Ramucirumab improved OS in patients with baseline ALBI grade 1 (HR 0.605 [0.445–0.824]) and ALBI grade 2 (HR 0.814 [0.630–1.051]). Conclusions Compared with placebo, ramucirumab did not negatively impact liver function and improved survival irrespective of baseline ALBI grade. Lay summary Hepatocellular carcinoma is the third leading cause of cancer-related death worldwide. Prognosis is affected by many clinical factors including liver function both before and during anticancer treatment. Here we have used a validated approach to assess liver function using 2 laboratory parameters, serum albumin and bilirubin (ALBI), both before and during treatment with ramucirumab in 2 phase III placebo-controlled studies. We confirm the practicality of using this more simplistic approach in assessing liver function prior to and during anticancer therapy, and demonstrate ramucirumab did not impair liver function when compared with placebo.

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Section: Discussionmentioning

confidence: 99%

Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

et al. 2021

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“…The use of adjuvant therapy may reduce this amount of recurrence. There is a strong argument for combined therapy of immunotherapy and surgery and/or locoregional treatment because of the treatment-induced reduction of tumorassociated antigens seen in other solid tumors (28). Amongst the several trials of HCC therapy designed to assess the safety and efficacy of adjuvant treatment in patient at significant recurrence risk after resection or ablation.…”

Section: Ongoing and Future Studiesmentioning

confidence: 99%

Checkpoint inhibitors: literature review of new treatments for hepatocellular carcinoma

Biglow¹,

Ashraf²,

Alsharedi³

2021

Stem Cell Investig

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“…By preventing B7 and CD28 ligation, CTLA-4 suppresses signal 2 in the antigen presenting cell—T cell interaction thereby leading to T-cell suppression; in this setting, anti-CTLA-4 releases this checkpoint, resulting in enhanced anti-tumor immunity [ 20 ]. To date ipilimumab and tremelimumab are the two anti-CTLA-4 agents approved for use in advanced cancer and among them, tremelimumab was the first immune checkpoint inhibitor to be tested in HCC [ 21 ]. Another open-label study of 19 patients showed similar results (ORR 26%, median time to response (mTTP) 7.4 mo, mOS 12.3 mo) [ 22 ].…”

Section: Indirect Immunotherapy: Immune Checkpoint Inhibitorsmentioning

confidence: 99%

Immuno-Oncotherapeutic Approaches in Advanced Hepatocellular Carcinoma

et al. 2020

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Advanced hepatocellular carcinoma has limited treatment options, but there has been extensive growth recently with cabozantinib, regorafenib, lenvatinib, nivolumab, atezolizumab, and bevacizumab, which are some of the treatments that have received FDA approval just over the last three years. Because HCC tumor microenvironment is potentially immunogenic and typically characterized by inflammation, immunotherapy has been proposed as a potential novel therapeutic approach, which has prompted studies in advanced HCC patients investigating various immune-therapeutic strategies such as CAR-T cell therapy, checkpoint inhibitors, and onco-vaccines. The anti-PD-1 checkpoint inhibitors nivolumab and pembrolizumab have been FDA approved as a second line treatment in patients who progressed or are intolerant to Sorafenib. To build up on the success of PD-1 monotherapy, combinatorial regimens with PD-1/PD-L1 inhibitors plus VEGF targeted agents have shown positive results in various malignancies including HCC. The combination of atezolizumab plus bevacizumab is the new addition to the HCC treatment armamentarium following a pivotal study that demonstrated an improvement in OS over frontline sorafenib. Other novel immune-based approaches and oncolytic viruses are in the early phases of clinical evaluation. These innovative approaches enhance the intensity of cancer-directed immune responses and will potentially impact the outlook of this aggressive disease.

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FRI-499-Efficacy and hepatic safety of nivolumab treatment in patients with Child-Pugh B disease and advanced hepatocellular carcinoma in CheckMate 040

Cited by 5 publications

References 0 publications

Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Effect of ramucirumab on ALBI grade in patients with advanced HCC: Results from REACH and REACH-2

Checkpoint inhibitors: literature review of new treatments for hepatocellular carcinoma

Immuno-Oncotherapeutic Approaches in Advanced Hepatocellular Carcinoma

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