Table 3.
Studies of Tyrosine Kinase Inhibitors in HER2 exon 20 mutation NSCLC.
| Drug | Trial | NSCLC population (n) | Overall Response Rate | Median PFS (Months) | Median OS (Months) | Ref |
|---|---|---|---|---|---|---|
| pyrotinib | phase II |
HER2 exon 20 mutation (n = 15) |
53.3% | 6.4 | n/a | [30] |
| pyrotinib | phase II |
HER2 mutation (n = 60; HER2 exon 20 mutation n = 56) |
30% | 6.9 | 14.4 | [31] |
| pyrotinib | phase II |
HER2 mutation (n = 78, HER2 exon 20 mutation = 62) |
19.2% | 5.6 | 10.5 | [32] |
| pyrotinib | phase II |
HER2 amplification (n = 27) |
22.2% | 6.3 | 12.5 | [33] |
| poziotinib | phase II |
HER2 exon 20 mutation (n = 30) |
27% | 5.5 | 15 | [34] |
| poziotinib | phase II (ZENITH20) |
HER2 exon 20 mutation (n = 90) |
27.8% | 5.5 | n/a | [35] |
| tarloxotinib | phase II (RAIN-701) |
EGFR Exon 20 insertion, HER2 activating mutation, or any solid tumors with NRG1, EGFR, HER2 or HER4 fusion (n = 23; HER2 n = 11) |
HER2 cohort: 22% | n/a | n/a | [36] |
| afatinib | phase II (NICHE) |
HER2 exon 20 mutation(n = 13) | 8% | 15.9 weeks | 56.0 weeks | [37] |
| afatinib ± paclitaxel | phase II | EGFR and HER2 (n = 41; HER2 exon 20 mutation n = 7) |
afatinib HER2: 0% afatinib + paclitaxel HER2: 33.3% | afatinib HER2: 17 weeks afatinib + paclitaxel (EGFR and HER2): 6.7 weeks |
n /a | [38] |
| neratinib ± TEM | phase II (PUMA-NER-4201) |
HER2 exon 20 mutation (n = 60) |
neratinib: 0% neratinib + TEM: 19% | neratinib: 3.0 neratinib + TEM: 4.1 |
neratinib: 10.0 neratinib + TEM: 15.8 | [39] |
| dacomitinib | phase II | HER2 exon 20 mutation (n = 26) or amplification (n = 4) |
HER2 exon 20 mutation: 12% HER2 amplification: 0% |
HER2 exon 20 mutation: 3.0 HER2 amplification: n/a a |
HER2 exon 20 mutation: 9.0 HER2 amplification: n/a a |
[40] |
PFS: progression free survival; OS: overall survival; IHC: immunohistochemistry; n/a: not available; TEM: temsirolimus. a Range for PFS was 1–5 months, and range for OS was 5–22 months.