Table 2.
Monoclonal antibodies in patients with NSCLC harboring HER2 aberrations. NA; not available; NR, not reached; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; ELISA, enzyme-linked immunosorbent assay; NGS, next-generation sequencing; ORR, objective response rate; PFS, progression-free survival; OS, overall survival; AE, adverse event.
| Reference | Agent | Study | N | Previous Treatment Type; N (%) |
HER2 Positivity Definition (Method) |
ORR N (%) |
PFS Median (95% CI) |
OS Median (95% CI) |
All-Grade AEs (%) |
|---|---|---|---|---|---|---|---|---|---|
| Kinoshita et al. [79] | Trastuzumab | Phase II, Single-arm | 10 | Yes, systemic therapy; 10 (100.0) |
Overexpression/ amplification (IHC3+, IHC2+/FISH+; NA), activating mutation (NA; NA) |
0/10 (0) | 5.2 months (1.4–6.3) |
– | – |
| Gatzemeier et al. [80] | Cisplatin, gemcitabine ± trastuzumab | Phase II, Randomized | 101 (50/101 cisplatin, gemcitabine and trastuzumab; 51/101 cisplatin, gemcitabine) |
No; 0 (0) | Overexpression/ amplification (IHC2-3+, FISH+, ELISA+; local) |
18/50 (36.0); 21/51 (41.2) |
6.1 months (0.1–19.6); 7.0 months (6.0–7.7) |
12.2 months (0.1–19.6); NR |
Nausea (74.0), vomiting (46.0), fatigue (42.0) |
| Langer et al. [81] | Carboplatin, paclitaxel, trastuzumab | Phase II, Single-arm | 53 | No; 0 (0) | Overexpression/ amplification (IHC1-3+; local) |
13/53 (24.5) | 3.3 months (NA) |
10.1 months (6.7–14.6) |
Anemia (99.0), fatigue (71.0), sensory neuropathy (65.0) |
| Hainsworth et al. [82] | Trastuzumab, pertuzumab | Phase II, Basket | 30 (16/30 HER2 overexpression/ amplification; 14/30 HER2 mutation) |
Yes, systemic therapy; NA |
Overexpression/ amplification (IHC3+, FISH+; local); exon 20 mutation (NGS; local) |
5/30 (16.7) [2/13 (15.4); 3/14 (21.4)] |
– | – | – |
| Hotta et al. [84] | T-DM1 | Phase II, Single-arm | 15 | Yes, systemic therapy; 15 (100.0) |
Overexpression/ amplification (IHC3+, IHC2+/FISH+; central), exon 20 mutation (NGS; central) |
1/15 (6.7) | 2 months (1.4–4.0) |
10.9 months (4.4–12.0) |
– |
| Li et al. [85] | T-DM1 | Phase II, Single-arm | 49 (11/49 HER2 amplification; 28/49 HER2 mutation) |
Yes, systemic therapy; 49 (100.0) |
Activating mutation (NGS; local) |
25/49 (51.0) [6/11 (54.5); 14/28 (50.0)] |
5 months (3.5–5.9) |
– | Elevated LFTs (63.3), thrombocytopenia (30.6), nausea (28.6) |
| Peters et al. [87] | T-DM1 | Phase II, Single-arm | 49 (29/49 HER2 IHC2+; 20/49 HER2 IHC3+) |
Yes, systemic therapy; 49 (100.0) |
Overexpression (IHC3+, IHC2+; central) |
4/49 (8.2) [0/29 (0); 4/20 (20.0)] |
2.6 months (1.4–2.8) |
12.2 (4.7–23.6) |
Infusion reaction (14.3), peripheral neuropathy (14.3), hemorrhage (14.3) |
| Tsurutani et al. [89] | T-Dxd | Phase I, Single-arm | 18 | Yes, systemic therapy; 18 (100.0) |
Overexpression/ amplification (IHC1+, FISH+, NGS; local) |
10/18 (55.6) | 11.3 months (5.5–14.1) |
17.3 months (17.3-NR) |
Nausea (74.6), vomiting (52.6), anemia (39) |
| Li et al. [53] | T-Dxd | Phase II, Two arms | 49 HER2 overexpression; 91 HER2 mutations |
Yes, systemic therapy; 140 (100.0) |
Activating mutation (NGS; local) | 12/49 (24.5); 50/91 (54.9) |
5.4 months (2.8–7.0); 8.2 months (6.0–11.9) |
NA; 17.8 months (13.8–22.1) |
Nausea (73.0), fatigue (53.0), alopecia (46.0) |