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Table 1 Basic characteristics of the 19 eligible studies

From: EGFR gene copy number as a predictive biomarker for the treatment of metastatic colorectal cancer with anti-EGFR monoclonal antibodies: a meta-analysis

Study Design  N   KRAS  mutation Agent; treatment modality Line Response criteria Tumor sample GCN assay
Bengala 200925 Retrospective 55 36.5 % Cmab/Pmab; CT NA NA NA FISH
Campanella 201026 Retrospective 88 37.7 % Cmab; mixed Mixed RECIST NA FISH
Cappuzzo 200823 Retrospective 85 NA Cmab; CT ≥2nd RECIST Mixed FISH
Frattini 200727 Retrospective 27 37.0 % Cmab; CT Mixed RECIST Primary FISH
Gevorgyan 200728 Retrospective 40 NA Cmab; CT NA NA Primary FISH
Goncalves 200829 Retrospective 29 44.8 % Cmab; CT ≥2nd WHO Mixed FISH
Italiano 200815 Retrospective 41 NA Cmab; CT NA RECIST Primary FISH
Khambata-Ford 200730 Prospective 56 34.6 % Cmab; MT ≥2nd WHO Metastatic Q-PCR
Laurent-Puig 200916 Retrospective 96 0 % Cmab; CT ≥2nd RECIST Mixed FISH + CISH
Lievre 200631 Retrospective 30 43.3 % Cmab; CT ≥2nd RECIST Primary CISH
Mancuso 200832 Retrospective 31 32.3 % Cmab; NA NA NA NA FISH
Moroni 200514 Retrospective 29 31.0 % Cmab/Pmab; mixed Mixed RECIST Primary FISH
Perrone 200924 Retrospective 31 24.1 % Cmab; CT ≥2nd RECIST Mixed FISH
Personeni 200833 Retrospective 87 33.3 % Cmab; mixed ≥3rd RECIST NA FISH
Razis 200834 Retrospective 66 NA Cmab; CT ≥2nd NA Metastatic FISH
Sartore-Bianchi 200717 Retrospective 58 NA Pmab; MT ≥2nd RECIST NA FISH
Sastre 200935 Prospective 36 21.7 % Cmab; MT 1st WHO NA FISH
Scartozzi 200936 Retrospective 37 0 % Cmab; CT ≥2nd RECIST Primary FISH
Tol 201037 Retrospective 155 0 % Cmab; CT 1st RECIST Primary FISH
Study Criteria for GCN+ GCN + %
Bengala 200925 Gene copies/nucleus ≥ 2.9 30.9
Campanella 201026 Polysomy: CEP7 ≥ 3; amplification: gene/CEP7 ≥ 2.0 68.2
Cappuzzo 200823 Gene copies/nucleus ≥2.92* 50.6
Frattini 200727 High polysomy: CEP7 > 4 in ≥ 50 % of cells; amplification: gene/CEP7 > 3 in ≥ 10 % of cells 88.9
Gevorgyan 200728 High polysomy: ≥ 4 gene copies in ≥ 40 % of cells; amplification: gene clusters, gene/CEP7 ≥ 2, or ≥ 15 gene copies in ≥ 10 % of cells 20.0
Goncalves 200829 High polysomy: ≥ 4 gene copies in ≥ 40 % of cells and gene/CEP7 ≤ 2; amplification: gene/CEP7 ≥ 2 or ≥ 15 gene copies in ≥ 10 % of cells 6.9
Italiano 200815 High polysomy: ≥ 4 gene copies in ≥ 40 % of cells; amplification: gene/CEP7 ≥ 2, or ≥ 15 gene copies in ≥ 10 % of cells 19.5
Khambata-Ford 200730 NA 7.1
Laurent-Puig 200916 High polysomy: ≥ 4 gene copies in ≥ 40 % of cells; amplification: gene clusters, gene/CEP7 ≥ 2, or ≥ 10 gene copies in ≥10 % of cells 17.7
Lievre 200631 Amplification: ≥ 6 gene copies in > 50 % of cells, or gene clusters 10.0
Mancuso 200832 Gene copies/nucleus ≥ 3 58.1
Moroni 200514 Gene copies/nucleus ≥ 3 31.0
Perrone 200924 Gene copies/nucleus ≥ 2.79* 74.2
Personeni 200833 Gene copies/nucleus ≥ 2.83* 37.9
Razis 200834 gene/CEP7 > 1.2 7.6
Sartore-Bianchi 200717 Polysomy: gene copies/nucleus ≥ 3; amplification: gene/CEP7 ≥ 2; in ≥ 43 % of cells 32.8
Sastre 200935 High polysomy: ≥ 4 gene copies in ≥ 40 % of cells; amplification: gene/CEP7 ≥ 2, or ≥ 15 gene copies in ≥ 10 % of cells 30.6
Scartozzi 200936 Gene copies/nucleus ≥ 2.6* 40.5
Tol 201037 Gene copies/nucleus ≥ 3, or gene/CEP7 ≥ 2 15.3
  1. N, sample size; GCN, gene copy number; GCN+, increased gene copy number; Cmab, cetuximab; Pmab, panitumumab; CT, combination therapy; NA, not available; RECIST, Response Evaluation Criteria in Solid Tumors; FISH, fluorescent in situ hybridization; CEP7, chromosome 7; WHO, World Health Organization criteria; MT, monotherapy; Q-PCR, quantitative polymerase chain reaction; CISH, chromogenic in situ hybridization.
  2. * the cutoff point was identified by Receiver Operating Characteristics analysis.