Dataset Information

Adjuvant and Neoadjuvant Treatments for Resectable Hepatocellular Carcinoma.

ABSTRACT:

Purpose of review

This review provides an update on the developments of adjuvant and neoadjuvant liver-directed and systemic therapy options for patients with resectable hepatocellular carcinoma.

Recent findings

Data on liver-directed treatment in the adjuvant and neoadjuvant settings are sparse and results are conflicting; many studies suggest that optimizing patient selection criteria is a key milestone required to improve study design and clinical benefit to patients. Systemic treatment options are primarily focused on investigation of anti-PD-1/L1 immunotherapeutic agents, either alone or in combination with other drugs. Numerous clinical trials in both adjuvant and neoadjuvant settings are in progress. Exploration of liver-directed and systemic treatment options for adjuvant and neoadjuvant treatment of patients with resectable hepatocellular carcinoma has the potential to improve clinical outcomes for this patient population.

SUBMITTER: Crook CJ

PROVIDER: S-EPMC10556166 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Adjuvant and Neoadjuvant Treatments for Resectable Hepatocellular Carcinoma.

Crook Christiana J CJ Li Daneng D

Current oncology reports 20230909 10

<h4>Purpose of review</h4>This review provides an update on the developments of adjuvant and neoadjuvant liver-directed and systemic therapy options for patients with resectable hepatocellular carcinoma.<h4>Recent findings</h4>Data on liver-directed treatment in the adjuvant and neoadjuvant settings are sparse and results are conflicting; many studies suggest that optimizing patient selection criteria is a key milestone required to improve study design and clinical benefit to patients. Systemic ...[more]

PMID: 37688739

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Project description:BackgroundSurgical resection of early stage hepatocellular carcinoma is standard clinical practice; however, most tumours recur despite surgery, and no perioperative intervention has shown a survival benefit. Neoadjuvant immunotherapy has induced pathological responses in multiple tumour types and might decrease the risk of postoperative recurrence in hepatocellular carcinoma. We aimed to evaluate the clinical activity of neoadjuvant cemiplimab (an anti-PD-1) in patients with resectable hepatocellular carcinoma.MethodsFor this single-arm, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma (stage Ib, II, and IIIb) were enrolled and received two cycles of neoadjuvant cemiplimab 350 mg intravenously every 3 weeks followed by surgical resection. Eligible patients were aged 18 years or older, had confirmed resectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0 or 1, and adequate liver function. Patients were excluded if they had metastatic disease, if the surgery was not expected to be curative, if they had a known additional malignancy requiring active treatment, or if they required systemic steroid treatment or any other immunosuppressive therapy. After resection, patients received an additional eight cycles of cemiplimab 350 mg intravenously every 3 weeks in the adjuvant setting. The primary endpoint was significant tumour necrosis on pathological examination (defined as >70% necrosis of the resected tumour). Secondary endpoints included delay of surgery, the proportion of patients with an overall response, change in CD8+ T-cell density, and adverse events. Tumour necrosis and response were analysed in all patients who received at least one dose of cemiplimab and completed surgical resection; safety and other endpoints were analysed in the intention-to-treat population. Patients underwent pre-treatment biopsies and blood collection throughout treatment. This trial is registered with ClinicalTrials.gov (NCT03916627, Cohort B) and is ongoing.FindingsBetween Aug 5, 2019, and Nov 25, 2020, 21 patients were enrolled. All patients received neoadjuvant cemiplimab, and 20 patients underwent successful resection. Of the 20 patients with resected tumours, four (20%) had significant tumour necrosis. Three (15%) of 20 patients had a partial response, and all other patients maintained stable disease. 20 (95%) patients had a treatment-emergent adverse event of any grade during the neoadjuvant treatment period. The most common adverse events of any grade were increased aspartate aminotransferase (in four patients), increased blood creatine phosphokinase (in three), constipation (in three), and fatigue (in three). Seven patients had grade 3 adverse events, including increased blood creatine phosphokinase (in two patients) and hypoalbuminaemia (in one). No grade 4 or 5 events were observed. One patient developed pneumonitis, which led to a delay in surgery by 2 weeks.InterpretationThis report is, to our knowledge, the largest clinical trial of a neoadjuvant anti-PD-1 monotherapy reported to date in hepatocellular carcinoma. The observed pathological responses to cemiplimab in this cohort support the design of larger trials to identify the optimal treatment duration and definitively establish the clinical benefit of preoperative PD-1 blockade in patients with hepatocellular carcinoma.FundingRegeneron Pharmaceuticals.

Project description:BackgroundThe prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) is extremely poor. The clinical outcome of preoperative radiotherapy (RT) is still controversial. This study aimed to compare the clinical outcomes of combined neoadjuvant RT and hepatectomy with hepatectomy alone for HCC with PVTT.MethodsComprehensive database searches were performed in PubMed, the Cochrane Library, EMBASE, and the Web of Science to retrieve studies published from the database creation to July 1, 2020. Only comparative studies that measured survival between neoadjuvant RT followed by hepatectomy and hepatectomy alone were included. The characteristics of the included studies and patients were extracted, and the included data are presented as relative ratio (RR) estimates with 95% confidence intervals (CIs) for all outcomes. The RRs of each study were pooled using a fixed or random effects model with Review Manager (the Cochrane Collaboration, Oxford, UK) version 5.3. The response rate to RT and the overall survival (OS) rate in neoadjuvant RT followed by hepatectomy and hepatectomy alone were measured.ResultsOne randomized and two non-randomized controlled trials with 302 patients were included. Most patients were classified as Child-Pugh A, and Type II and III PVTT were the most common types. After RT, 29 (22.8%) patients were evaluated as partial response (PR) and had a positive RT response, but nine (7.1%) had progressive disease (PD). Neoadjuvant RT followed by hepatectomy was received by 127 (42.1%) patients after excluding 15 (5.0%) patients with severe complications or PD after RT, and 160 (53.0%) patients received hepatectomy alone. In the randomized controlled trial (RCT), the 1-year OS rate in the neoadjuvant RT group and the surgery alone group was 75.2% and 43.1%, respectively (P<0.001). In the two non-randomized studies, a meta-analysis with a fixed effects model showed a longer OS in patients undergoing neoadjuvant RT followed by hepatectomy compared with hepatectomy alone at 1-year follow-up (RR =2.02; 95% CI: 1.45-2.80; P<0.0001).ConclusionsThis systematic review showed that neoadjuvant RT followed by hepatectomy in patients with resectable HCC and PVTT was associated with a longer OS than patients who received hepatectomy alone.

Dataset Information

Adjuvant and Neoadjuvant Treatments for Resectable Hepatocellular Carcinoma.

Purpose of review

Recent findings

Publications

Adjuvant and Neoadjuvant Treatments for Resectable Hepatocellular Carcinoma.

Similar Datasets

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