Systematic review and characteristics of the included studies
To determine the efficacy of safety of HER2-ADCs in GC/GEJC patients, we first aimed to identify studies published on the topics of ‘gastric cancer’, ‘gastro-oesophageal junction cancer’, ‘HER2’ and ‘antibody-drug conjugates’ for our meta-analysis. Following our retrieval strategy, 325 records were initially identified in the selected databases. After removing 105 , based on the titles and abstracts, 185 articles were excluded due to irrelevant trials, reviews, meta-analyses or other types mentioned in the exclusion criteria, leaving 35 trials considered eligible. After full-text review and removal of duplicate datasets and studies without data available, 27 studies were further excluded due to the type of publication; 8 studies were finally included27, 30-36. The flowchart of the detailed retrieval process is shown in Figer 1. As the DESTINY-Gastric01 trial (NCT03329690) consisted of one primary cohort and two exploratory cohorts involving patients with different HER2-expression statuses, the Shitara 2020 and Yamaguchi 2023 papers were considered two separate studies in this meta-analysis.
A total of 871 patients were enrolled in the 8 studies, and the sample sizes ranged from 17 to 345. Among the included patients, 590 (67.7%) patients were identified HER2-positive (IHC 3+ or IHC 2+/ ISH-positive) and 54 (6.2%) patients were identified HER2-low (IHC 2+/ISH-negative or IHC 1+). Additionally, of the HER2-positive patients, 528 (89.5%) had previously trastuzumab therapy. Among all anti-HER2 ADCs applied in the eligible trials, except T-DXd, which was used as an intervention regimen in 4 studies, the other medications including T-DM1, ARX788, SYD985 and RC48 were used in only one study each. The complete characteristics of all included studies are presented in Table 1.
Table 1. Characteristics of the included studies