Table 1.
Characteristics of studies included in the meta-analysis.
| Study | Sample size | Median age (years) | Male sex (%) | HER2 detection method and positivity criteria | Therapy type | LOT | Median follow-up (months) | Outcome measures |
|---|---|---|---|---|---|---|---|---|
| Yagisawa 202127 Sawada 201812 |
54 | 65 (HER2+) 64 (HER2-) |
20 (HER2+) 61.2 (HER2-) |
IHC 3+ or 2+ and FISH HER2/CEP17 ≥2.0 | Anti-EGFR alone Anti-EGFR + IRI |
1-5L | 101.8 | PFSa, ORR, OSa |
| Jeong 2016/201715,25 | 142 | 56 | 70.4 | IHC 3+ or 2+ or IHC scores 3+ or 2+ in ≥50% of cells (HERACLES criteria) and SISH HER2/CEP17 ratio >2.2 | CET CET + IRI |
2-4L+ | 13.2 | PFS, OS |
| Sartore-Bianchi 2018/201911,26 | 216 | 58.9b (HER2+); 58.4b (HER2-) |
75 (HER2+); 68.1 (HER2-) |
IHC scores 3+ or 2+ in ≥50% of cells and FISH HER2/CEP17 ≥2.0 in ≥50% of cells (HERACLES criteria) | Anti-EGFR monotherapy+/- CTX | 1-5L | 50.1 (HER2+); 83.7 (HER2-) |
PFS, ORR, OSa |
| Raghav 2016/201916,28 | 70 | 57 | 54.3 | ISH positive (HER2/CEP17 ≥2) and NGS ≥4 gene copies identified by an in-house algorithmc | CET or PAN CET/PAN + IRI/OX-based CTX |
2L/3L | 24d | PFS |
| Khelwatty 202129 | 144 | NR | 70 | IHC score 3+ localized membranous/cytoplasmic HER2 expression c | CET + FOLFOX CET + FOLFIRI |
1L | 48 (OS 28.5, PFS 19) |
PFS, ORR, OSe |
aHR calculated from Kaplan-Meier curves.
bMean age.
cResults by NGS detection method and localized membranous HER2 expression were considered for the meta-analyses to be more robust based on consultations with clinical experts.
dAssumed from KM curve follow-up.
eThe HR for OS in Khelwatty et al29 was inconsistent, the lower CI was higher than HR value (HR, 0.21 [95% CI, 0.62-0.73]), and it was excluded from the OS analysis. Study authors were contacted to clarify the data but no response was received.
Abbreviations: 1L/2L/3L/4L/5L, first-/ second-/ third-/ fourth-/ fifth-line; CEP, chromosome enumeration probe; CET, cetuximab; CTX, chemotherapy; DISH, dual in situ hybridization; EGFR, epidermal growth factor receptor; FISH, fluorescence in situ hybridization; FOLFIRI, folinic acid, fluorouracil, irinotecan; FOLFOX, folinic acid, fluorouracil, oxaliplatin; HER2+, HER2-positive group; HER2-, HER2-negative group; IHC, immunohistochemistry; IRI, irinotecan; ISH, in situ hybridization; LOT, line of treatment; NGS, next-generation sequencing; NR, not reported; ORR, overall response rate; OS, overall survival; OX, oxaliplatin; PAN, panitumumab; PFS, progression-free survival; SISH, silver in situ hybridization.