Table 3.
Efficacy by centrally assessed exploratory biomarker in patients treated with neratinib + fulvestrant + trastuzumab
| Centrally assessed exploratory biomarker | No. of patients | ORR, n (%) | CBR, n (%) | Median PFS, months (95% CI) |
|---|---|---|---|---|
|
| ||||
| NGS mutation | ||||
| HER2 | ||||
| Yes | 48 | 20 (42) | 28 (58) | 10.2 (6.1–18.6) |
| No | 6 | 0 | 0 | 4.2 (1.8–6.2) |
| Insufficient sample | 3 | 2 (67) | 3 (100) | 12.7 (8.2–12.7) |
| HER2 and ERBB3 | 10 | 4 (40) | 6 (60) | 25.7 (1.0-NE) |
| HER2 and ESR1 | 6 | 3 (50) | 4 (67) | 8.3 (1.9–18.6) |
| HER2 and CDH1 | 27 | 11 (41) | 15 (56) | 15.1 (2.4–18.6) |
| HER2 and TP53 | 13 | 3 (23) | 5 (38) | 6.0 (1.9–8.3) |
| HER2 and PIK3CA | 19 | 4 (21) | 10 (53) | 7.8 (2.2–10.2) |
| HER2 and none of above | 7 | 4 (57) | 4 (57) | NE (3.9-NE) |
| IHC category | ||||
| 0/1+ | 10 | 2 (20) | 4 (40) | 7.0 (1.8-NE) |
| 2+ | 21 | 9 (43) | 12 (57) | 8.3 (2.6–18.0) |
| 3+ | 1 | 0 | 0 | 3.9 (NE-NE) |
| Insufficient tissue | 25 | 11 (44) | 15 (60) | 10.2 (4.3–18.6) |
| FISH category | ||||
| Amplified | 10 | 3 (30) | 5 (50) | 6.1 (1.0-NE) |
| Non-amplified | 20 | 8 (40) | 11 (55) | 8.5 (4.1–18.0) |
| Insufficient tissue | 27 | 11 (41) | 15 (56) | 8.3 (4.2–18.6) |
| Overall HER2 status (IHC 3+ or FISH amplified) | ||||
| Positive | 10 | 3 (30) | 5 (50) | 6.1 (1.0-NE) |
| Negative | 20 | 8 (40) | 11 (55) | 8.5 (4.1–18.0) |
| Insufficient tissue | 27 | 11 (41) | 15 (56) | 8.3 (4.2–18.6) |
| Molecular subtype | ||||
| Luminal A | 4 | 0 | 1 (25) | 3.1 (1.0-NE) |
| Luminal B | 4 | 2 (50) | 2 (50) | 14.0 (2.0–25.7) |
| HER2 enriched | 11 | 5 (45) | 8 (73) | 8.3 (1.9–10.2) |
| Insufficient tissue | 38 | 15 (39) | 20 (53) | 8.3 (4.7–18.0) |
CBR, clinical benefit rate; CI, confidence interval; FISH, fluorescence in situ hybridization; IHC, immunohistochemistry; NE, not estimable; NGS, next-generation sequencing; ORR, objective response rate; PFS, progression-free survival.