Background
Phase III noninferiority trial, N=766 (382 THP, 384 TCbHP), stage II-III HER2+ breast cancer, age ≥18 years, previously untreated. Tests whether carboplatin can be omitted from neoadjuvant dual HER2-blockade chemotherapy without compromising pathologic complete response.
Interventions and follow up
Arm A: Taxane (docetaxel, paclitaxel, or nab-paclitaxel) + trastuzumab + pertuzumab (THP)
Arm B: Carboplatin + taxane + trastuzumab + pertuzumab (TCbHP)
Primary endpoint: Pathologic complete response (pCR) in breast and axilla (ypT0/is ypN0)
mFollow up: Primary analysis at end of neoadjuvant treatment
Arm B: Carboplatin + taxane + trastuzumab + pertuzumab (TCbHP)
Primary endpoint: Pathologic complete response (pCR) in breast and axilla (ypT0/is ypN0)
mFollow up: Primary analysis at end of neoadjuvant treatment
Results
pCR rate: THP 64.1% vs TCbHP 65.9%, absolute difference -1.8% (95% CI, -8.5 to 5.0), odds ratio 0.93 (95% CI, 0.69-1.25), P=.0089 (noninferiority met)
Grade 3-4 adverse events (overall): THP 20.7% vs TCbHP 34.6%, P<.001
Grade 3-4 adverse events (overall): THP 20.7% vs TCbHP 34.6%, P<.001
Adverse events
Hematologic (Grade 3-4): neutropenia 6.8% (THP) vs 16.4% (TCbHP); leukopenia 5.5% vs 14.8%
Gastrointestinal (Grade 3-4): diarrhea 2.6% vs 4.2%; no treatment-related deaths in either arm
Gastrointestinal (Grade 3-4): diarrhea 2.6% vs 4.2%; no treatment-related deaths in either arm
Conclusions
Taxane + dual HER2 blockade without carboplatin provided noninferior pCR and superior tolerability. Omitting carboplatin is applicable in HER2+ early breast cancer. The regimen-flexible approach allowing investigator choice of taxane may enhance real-world applicability.
Key Limitations
Noninferiority design with a large predefined margin may limit generalizability; restricted to stage II-III HER2+ disease; does not address efficacy across all patient subgroups or long-term disease-free/overall survival, which await longer follow-up.
Clinical Context
Establishes that carboplatin can be omitted from neoadjuvant HER2-directed therapy while maintaining pCR and reducing toxicity. Aligns with ASCO and ESMO de-escalation strategies in early HER2+ breast cancer, where taxane plus dual HER2 blockade (THP) is already an accepted neoadjuvant backbone, and supports lower-cost, better-tolerated regimens.