Table 1.
Clinical trials of anti-HER2 agents in NSCLC patients.
| References | Agents | Clinical trials | N | Population | HER2 alterations | ORR n (%) | Median PFS months, (95% CI) | Median OS months, (95% CI) |
|---|---|---|---|---|---|---|---|---|
| Langer et al. (45) | Trastuzumab + CT | Phase II study | 53 | Recurrent, Stage IIIB/IV NSCLC | HER2 positivity (1+ to 3+) | 13 (24.5) | 3.3 (NA) | 10.1 (6.7-14.6) |
| Gatzemeier et al. (46) | Trastuzumab + CT | Phase II study | 50 | Untreated stage IIIB/IV NSCLC | HER2 IHC 2+/3+ or serum HER2 ECD positive | 18 (36) | 6.1 (0.1-19.6) | 12.2 (0.1-19.6) |
| Hainsworth et al. (47) | Pertuzumab + Trastuzumab | Phase IIa basket study (MyPathway) | 16 | Refractory, metastatic NSCLC | HER2 amplification or overexpression | 2 (13) | NA | NA |
| 14 | HER2 mutation | 3 (21) | NA | NA | ||||
| Kinoshita et al. (48) | Trastuzumab | Phase II study (HOT1303-B) | 10 | NSCLC patients pretreated with ≥2 regimens | HER2 IHC 3+, IHC2+/DISH+ or mutation | 0 (0) | 5.2 (1.4-6.3) | NA |
| Mazieres et al. (49) | Pertuzumab + Trastuzumab + Docetaxel | Phase II study (IFCT-1703 R2D2) | 45 | Advanced NSCLC, progressed after ≥1 platinum-based treatment | HER2 mutation | 13 (29) | 6.8 (4.0-8.5) | 17.6 (11.6-18.9) |
| Peters et al. (51) | Afatinib | Global Named Patient Use Program | 28 | Heavily pretreated, stage IV NSCLC | HER2 mutation | 3/16 (19) a | NA | NA |
| Dziadziuszko et al. (52) | Afatinib | Phase II study (NICHE) | 13 | Pretreated, advanced NSCLC | HER2 mutation | 1 (7.7) | 3.7 (1.4-8.3) | 13.1 (3.8-NE) |
| Fan et al. (53) | Afatinib | Phase II study | 18 | Pretreated, advanced NSCLC | HER2 mutation | 0 (0) | 2.76 (1.87-4.60) | 10.02 (8.47-10.08) |
| Kris et al. (57) | Dacomitinib | Phase II study | 26 | Advanced NSCLC, 83% pretreated with CT | HER2 mutation | 3 (11.5) | 3 (2-4) | 9 (7-21) |
| 4 | HER2 amplification | 0 (0) | 1,1,5,5 | 5,7,15,22 | ||||
| Besse et al. (60) | Neratinib (N)±Temsiromilus (TEM) | Phase II study | 13 | Stage IIIB/IV NSCLC (N) | HER2 mutation | 0 (0) | 2.9 (1.4-NE) | NA |
| 14 | Stage IIIB/IV NSCLC (N + TEM) | 3 (21) | 4.0 (2.9-9.8) | |||||
| Gandhi et al. (61) | Phase II study (Expansion cohort) | 17 | Stage IIIB/IV NSCLC (N) | HER2 mutation | 0 (0) | 3.0 (1.4-6.9) | 10.0 (4.9-19.0) | |
| 43 | Stage IIIB/IV NSCLC (N + TEM) | 8 (19) | 4.1 (2.9-5.6) | 15.8 (10.8-19.5) | ||||
| Hyman et al. (62) | Neratinib | Phase II basket study (SUMMIT) | 26 | Pretreated, advanced NSCLC | HER2 mutation | 1 (3.8) | 5.5 (NA) | NA |
| Robichaux et al. (12) | Poziotinib | Phase II study | 12 | Metastatic, recurrent NSCLC | HER2 mutation | 5 (42) | 5.6 (NA) | NA |
| Prelaj et al. (66) | Poziotinib | Phase II study | 8b | Advanced NSCLC | HER2 mutation | 4 (50) | 5.6 (3.6-6.7) c | 9.5 (5.3-NE) c |
| Elamin et al. (67) | Poziotinib | Phase II study | 30 | Stage IV or recurrent NSCLC, 90% of patients were pretreated | HER2 mutation | 8 (27) | 5.5 (4.0-7.0) | 15 (9.0-NE) |
| Le et al. (68) | Poziotinib | Phase II study (ZENITH 20) | 90 | Pretreated, advanced NSCLC | HER2 mutation | 25 (27.8) | 5.5 (3.9-5.8) | NA |
| Cornelissen et al. (69) | 48 | Treatment naïve, advanced NSCLC | HER2 mutation | 21 (44) | 5.6 (NA) | NA | ||
| Wang et al. (70) | Pyrotinib | Phase II study | 15 | Pretreated, advanced NSCLC | HER2 mutation | 8 (53.3) | 6.4 (1.60-11.20) | 12.9 (2.05-23.75) |
| Song et al. (71) | Pyrotinib | Prospective, single-arm trial | 27 | Stage IIIB/IV NSCLC | HER2 amplification | 6 (22.2) | 6.3 (3.0-9.6) | 12.5 (8.2-16.8) |
| Zhou et al. (73) | Pyrotinib | Phase II study | 60 | Pretreated, advanced NSCLC | HER2 mutation | 18 (30) | 6.9 (5.5-8.3) | 14.4 (12.3-21.3) |
| Hotta et al. (81) | T-DM1 | Phase II study | 15 | Pretreated, advanced NSCLC | HER2 IHC 3+, IHC2+/FISH+ or mutation | 1 (6.7) | 2.0 (1.4-4.0) | 10.9 (4.4-12.0) |
| Li et al. (82) | T-DM1 | Phase II basket study | 18 | Advanced NSCLC, 83% pretreated with CT | HER2 mutation | 8 (44) | 5 (3-9) | NA |
| Peters et al. (83) | T-DM1 | Phase II study | 29 | Locally advanced or metastatic NSCLC, pretreated with ≥1 CT | HER2 IHC 2+ | 0 (0) | 2.6 (1.4-2.8) | 12.2 (3.8-23.3) |
| 20 | HER2 IHC 3+ | 4 (20) | 2.7 (1.4-8.3) | 15.3 (4.1-NE) | ||||
| Tsurutani et al. (86) | T-DXd | Phase I study | 18 | Pretreated, advanced or recurrent NSCLC | HER2 overexpression or mutation | 10 (55.6) | 11.3 (7.2-14.3) | NR (17.3-NE) |
| Nakagawa et al. (87) | T-DXd | Phase II study (DESTINY-Lung01) | 49 | Pretreated, metastatic NSCLC | HER2 overexpression | 12 (24.5) | 5.4 (2.8-7.0) | NA |
| Li et al. (88) | 91 | Pretreated, unresectable or metastatic NSCLC | HER2 mutation | 50 (55) | 8.2 (6.0-11.9) | 17.8 (13.8-22.1) |
N, number; ORR, objective response rate; PFS, progression-free survival; OS, overall survival; CT, chemotherapy; IHC, immunohistochemistry; ECD, extracellular domain; DISH, dual color in situ hybridization; FISH, fluorescence in situ hybridization; NA, not available; NE, not estimable; NR, not reached.
a
Tumor response data were available for 16 patients. bThis phase II study enrolled 30 patients, 22 had EGFR 20 exon mutations and 8 had HER2 mutations. cPFS and OS data were evaluated based on the whole cohort (n=30).