Table 1.
Description of HER2 mutations and clinical outcomes of patients treated with dacomitinib
|
HER2 mutation type Partial responses noted |
HER2 amplification status by FISH (HER2/CEP17 ratio) | Mutation Amino acid change (and nucleotide change) |
Alternate nomenclature (based on HGVS guidelines) |
Survival from start of dacomitinib (months) |
|---|---|---|---|---|
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 23 |
| Exon 20 insertion (12-bp duplication) | <2.0 | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 10 |
| Exon 20 insertion (12-bp duplication) | <2.0 | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 16 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 3 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 2 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 9 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 9 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 29 |
| Exon 20 insertion (12-bp duplication) | <2.0 | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 5 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 2+ |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 7 |
| Exon 20 insertion (12-bp duplication) | Not tested | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 14 |
| Exon 20 insertion (12-bp duplication) | <2.0 | p. A775_G776insYVMA (c. 2324_2325ins12) | p.Y772_A775dup (c.2313_2324dup) | 26+ |
| Exon 20 insertion (9-bp duplication) Partial response Duration 14 months |
<2.0 | p. P780_Y781insGSP (c. 2339_2340ins GGCTCCCCA) | p.G778_P780dup (c.2331_2339dup) |
27 |
| Exon 20 insertion (9-bp duplication) Partial response Duration 11 months |
<2.0 | p. P780_Y781insGSP (c. 2339_2340ins GGCTCCCCA) |
p.G778_P780dup (c.2331_2339dup) |
25+ |
| Exon 20 insertion (9 bp) | Not tested | Not specified | Nor specified | 4 |
| Exon 20 insertion (9 bp) | <2.0 | Not specified | Not specified | 8 |
| Exon 20 insertion (3 bp) | <2.0 | Not specified | Not specified | 3 |
| Exon 20 insertion (3 bp) | Not tested | p. G776 > VC (c.2326_2327insTGT) | p.G776delinsVC (c.2326_2327insTGT) |
21 |
| Exon 20 insertion (3 bp) | Not tested | p. G776 > VC (c.2326_2327insTGT) | p.G776delinsVC (c.2326_2327insTGT) |
2 |
| Exon 20 insertion | Not tested | Not specified | Not specified | 7 |
| Exon 20 insertion | <2.0 | Not specified | Not specified | 18+ |
| Exon 20 insertion | Not tested | Not specified | Not specified | 21+ |
| Exon 20 indel Partial response Duration 3+ months |
Not tested | p. M774delinsWLV (c.2320A > TGGCTGG) |
p. M774delinsWLV (c.2320delins TGGCTGG) |
23+ |
| Exon 20 indel | <2.0 | p. G776 > LC (c. 2326G > TTGT) |
p.G776delinsLC (c.2326delinsTTGT) |
9 |
| Exon 20 missense mutation | Not tested | p. V777L (c.2329G > T) | p. V777L (c.2329G > T) | 3 |
HGVS, Human Genome Variation Society.