PMID- 37886169
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231028
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 13
DP  - 2023
TI  - Efficacy and safety of zolbetuximab for first-line treatment of advanced Claudin 
      18. 2-positive gastric or gastro-esophageal junction adenocarcinoma: a systematic 
      review and meta-analysis of randomized controlled trials.
PG  - 1258347
LID - 10.3389/fonc.2023.1258347 [doi]
LID - 1258347
AB  - OBJECTIVE: Zolbetuximab is a "first-in-class" chimeric lgG1 monoclonal antibody 
      targeting Claudin18.2 (CLDN 18.2). In recent years, several important trials have 
      been published showing that zolbetuximab is associated with improved prognosis in 
      patients with advanced gastric or gastro-esophageal junction (G/GEJ) 
      adenocarcinoma. This promises great change to the current treatment landscape. 
      Therefore, we conducted a systematic review and meta-analysis to evaluate the 
      efficacy and safety of zolbetuximab for first-line treatment of advanced CLDN 18. 
      2-positive G/GEJ adenocarcinoma. METHODS: The following databases were searched 
      for relevant studies: PubMed, EMBASE, and Cochrane library (updated 10 June 
      2023). All randomized trials comparing zolbetuximab plus chemotherapy versus 
      first-line chemotherapy alone for first-line treatment of advanced CLDN 18. 
      2-positive G/GEJ adenocarcinoma were eligible for inclusion. Data were analyzed 
      using Review Manager 5.4.1 (Cochrane collaboration software). Primary outcomes 
      and measures included overall survival (OS), progression-free survival (PFS), 
      objective response rate (ORR), and adverse events (AEs). RESULTS: This systematic 
      review and meta-analysis included three randomized controlled studies involving 
      1,402 patients (699 receiving zolbetuximab plus chemotherapy and 703 receiving 
      chemotherapy alone). Compared with chemotherapy alone, zolbetuximab plus 
      chemotherapy significantly improved OS (HR = 0.73; 95% CI: 0.68-0.84) and PFS (HR 
      = 0.64; 95% CI: 0.50-0.82), but did not result in a higher ORR (RR = 0.92; 95% 
      CI: 0.82-1.03). Further analysis of CLDN 18.2 expression showed a more 
      significant benefit for OS (HR = 0.69; 95% CI: 0.55-0.87; p = 0.002) and PFS (HR 
      = 0.61; 95% CI: 0.44-0.84; p = 0.003) from zolbetuximab in patients with high 
      expression, while there was significant benefit in patients with lower 
      expression. In terms of AEs, zolbetuximab plus chemotherapy was associated with 
      higher risk of grade 3 and higher AEs, but increased risk of nausea and vomiting 
      were more common. CONCLUSION: This systematic review and meta-analysis revealed 
      that the effect of zolbetuximab plus chemotherapy was superior to that of 
      chemotherapy alone for first-line treatment of advanced CLDN 18.2-positive G/GEJ 
      adenocarcinoma. Thus, zolbetuximab plus chemotherapy represents a new first-line 
      treatment for these patients. Zolbetuximab plus chemotherapy was associated with 
      higher risk of grade 3 and higher AEs, but was generally manageable. SYSTEMATIC 
      REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero, identifier 
      (CRD42023437126).
CI  - Copyright (c) 2023 Liang, Liu, Li, Lai, Li, Wu, Zhang and Fang.
FAU - Liang, Zhanpeng
AU  - Liang Z
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Liu, Liwen
AU  - Liu L
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Li, Wenxia
AU  - Li W
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Lai, Huiqin
AU  - Lai H
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Li, Luzhen
AU  - Li L
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Wu, Jiaming
AU  - Wu J
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Zhang, Huatang
AU  - Zhang H
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
FAU - Fang, Cantu
AU  - Fang C
AD  - Department of Oncology, Zhongshan Hospital of Traditional Chinese Medicine 
      Affiliated to Guangzhou University of Traditional Chinese Medicine, Zhongshan, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20231009
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC10598679
OTO - NOTNLM
OT  - Claudin18.2
OT  - gastric or gastro-oesophageal junction adenocarcinoma
OT  - meta-analysis
OT  - targeted therapy
OT  - zolbetuximab
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/10/27 06:43
MHDA- 2023/10/27 06:44
PMCR- 2023/01/01
CRDT- 2023/10/27 04:33
PHST- 2023/07/13 00:00 [received]
PHST- 2023/09/15 00:00 [accepted]
PHST- 2023/10/27 06:44 [medline]
PHST- 2023/10/27 06:43 [pubmed]
PHST- 2023/10/27 04:33 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2023.1258347 [doi]
PST - epublish
SO  - Front Oncol. 2023 Oct 9;13:1258347. doi: 10.3389/fonc.2023.1258347. eCollection 
      2023.