This phase 2 study in patients with HER2-positive breast cancer and leptomeningeal metastases showed that tucatinib, trastuzumab, and capecitabine achieved a median overall survival of 10 months, exceeding historical controls. The regimen demonstrated a 38% objective response rate, improved neurological symptoms in 58% of patients, and was well tolerated with manageable adverse events.
Study
|
Phase 2, single-arm, nonrandomized, multicenter study [TBCRC049] |
| HER2-positive breast cancer with newly diagnosed leptomeningeal metastasis (LM) |
| Tucatinib + trastuzumab + capecitabine (n=17)
|
Efficacy
|
ORR (composite LM objective response): 38% (5/13 evaluable patients) |
| mOS: 10 mos [4.1-NR] |
| Median time to CNS progression: 6.9 mos [2.3-13.8] |
| 41% (6/17) patients alive at median follow-up of 18 mos |
| 58% (7/12) patients showed neurological symptom improvement |
| Clinical benefit (CR+PR+SD) in 100% (13/13 evaluable patients)
|
Safety
|
Grade 3 TEAEs: nausea and vomiting (1 patient), hand-foot syndrome (1 patient), liver function test elevation (3 patients) |
| Grade 4 TEAE: alanine aminotransferase elevation (1 patient), led to study discontinuation
|
Nat Cancer. Published online 2026 Mar 18
http://doi.org/10.1038/s43018-026-01120-7
Reviewed by Ulas D. Bayraktar, MD on Apr 10, 2026
