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Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer.

ABSTRACT: Claudin 18.2 (CLDN18.2) is a tight-junction protein. CLDN18.2-targeting strategy has cut a striking figure in CLDN18.2 positive patients with advanced gastric cancer. Zolbetuximab, the CLDN18.2 antibody, obtained a better clinical benefit in patients compared with the controlled. In phase II trials, combination treatment of epirubicin, oxaliplatin and capecitabine (EOX) + zolbetuximab achieved the optimal effects of overall survival which extended to 13.2 months with tolerable safety events, indicating its greater potential playing the second promising target in gastric cancer. This review will reveal the definitive clinical benefit CLDN18.2-targeting therapies have achieved and update the highlighting development (like chimeric antigen receptor T-cell immunotherapy) to CLDN18.2 positive patients. We then focus on 10 questions arisen from recent progress and anticipate to provide a future perspective for novel cancer treatment.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7219097 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer.

Zhang Jianwei J Dong Ruilan R Shen Lin L

Chinese journal of cancer research = Chung-kuo yen cheng yen chiu 20200401 2

Claudin 18.2 (CLDN18.2) is a tight-junction protein. CLDN18.2-targeting strategy has cut a striking figure in CLDN18.2 positive patients with advanced gastric cancer. Zolbetuximab, the CLDN18.2 antibody, obtained a better clinical benefit in patients compared with the controlled. In phase II trials, combination treatment of epirubicin, oxaliplatin and capecitabine (EOX) + zolbetuximab achieved the optimal effects of overall survival which extended to 13.2 months with tolerable safety events, ind ...[more]

PMID: 32410803

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Project description:BackgroundMultiple anti-programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors and zolbetuximab, an anti-claudin 18.2 antibody, have shown efficacy in the first-line treatment of HER2-negative gastric cancers. How to choose the best regimen remains an unsolved question.ObjectivesWe aimed to conduct a comparative analysis of the therapeutic advantages between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers.DesignNetwork meta-analysis was employed to systematically compare efficacy and safety data derived from various clinical trials.Data sources and methodsWe included phase III randomized controlled trials in PubMed, Embase, Web of Science, Cochrane Library, and major conference abstracts. Network meta-analysis was used to compare the efficacy of each first-line therapeutic agent and to indirectly compare immunotherapy with anti-claudin-18.2-targeted therapy.ResultsEight trials comprising a total of 6455 patients were included. For the overall survival (OS) analysis, no statistically significant differences were observed between pembrolizumab [hazard ratios (HR) = 1.00, 95% CI: 0.94-1.07], sintilimab (HR = 0.99, 95% CI: 0.89-1.09), sugemalimab (HR = 0.98, 95% CI: 0.87-1.10), tislelizumab (HR = 0.97, 95% CI: 0.87-1.09), zolbetuximab (HR = 0.98, 95% CI: 0.91-1.07), and nivolumab (HR = 1.00). For the progression-free survival (PFS) analysis, no statistically significant differences were observed between pembrolizumab (HR = 1.00, 95% CI: 0.93-1.06), sintilimab (HR = 0.91, 95% CI: 0.83-1.00), sugemalimab (HR = 0.92, 95% CI: 0.84-1.02), tislelizumab (HR = 0.93, 95% CI: 0.84-1.03), zolbetuximab (HR = 0.96, 95% CI: 0.88-1.05), and nivolumab (HR = 1.00). For the overall response rate analysis, all regimens presented similar effects on ORR. In addition, anti-claudin-18.2-targeted therapies presented similar OS (HR = 0.99, 95% CI: 0.95-1.04) and PFS (HR = 1.01, 95% CI: 0.91-1.12) compared to immunotherapy, although their toxicity profiles were distinct.ConclusionsOur network meta-analysis showed no significant difference in PFS, OS, or ORR between different checkpoint inhibitors or between immunotherapy and anti-claudin-18.2-targeted therapies in the first-line treatment of HER2-negative, unresectable, or metastatic gastric cancers.

Project description:To examine the prognostic value of claudin 18.2 (CLDN18.2) and human epidermal growth factor receptor-2 (HER-2) expression in patients with resected pancreatic ductal adenocarcinoma (PDAC). This study enrolled patients who underwent surgery and were diagnosed with PDAC at Suleyman Demirel University Hospital, Turkey between 2015 and 2019. Sixty-eight patients with resected PDAC treated at a medical oncology clinic were assessed. All patients were over the age of 18 years, underwent follow-up and treatment in our unit, and had pathology slides that we could access. Clinicopathological data were obtained from medical files, including the patients' age, sex, pathological parameters, and clinical stage according to the Eighth International Union against Cancer/American Joint Committee on Cancer. Patient survival and the period from the date of diagnosis to death were assessed in the follow-up data. There was no statistically significant difference between CLDN18.2 and HER-2 expression scores for samples and patient clinicopathological characteristics. No HER-2 expression scores of ≥2 were found in the samples. Only 25% (n = 17) of the samples had HER-2 expression scores of +1. CLDN18.2 expression was detected in 54.4% (n = 37) of the patient samples. CLDN18.2 expression scores were +1 in 30.8% (n = 21) of the patient samples, +2 in 16.2% (n = 11), and +3 in 7.4% (n = 5). When CLDN18.2 and HER-2 expression were compared, a statistically significant difference and moderate positive correlation were observed. No significant relationship between HER-2 expression and survival was observed in the survival analysis of PDAC patients; however, high CLDN18.2 expression was related to longer overall survival. Our study is the third to research CLDN18.2 expression in PDAC. HER-2 expression is low and CLDN18.2 expression is high in patients with PDAC. HER-2 expression is not related to overall survival but CLDN18.2 is related and may be used as a prognostic marker in patients with PDAC.

Dataset Information

Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer.

Publications

Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric cancer.

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