- After a 3-year follow-up, no efficacy improvements were observed for an anthracyclines-containing regimen in patients with stage II-III HER2-positive breast cancer (BC).
- The addition of anthracyclines is associated with clinically relevant toxicity.
- A neoadjuvant anthracyclines-free regimen with dual HER2-blockade should be considered in all stage II-III HER2-positive BC patients.
Why this matters
- The value of anthracyclines in the management of early HER2-positive BC is uncertain and long-term follow-up data are needed.
- Anthracycline use is still common in high-risk HER2-positive BC.
- The randomized phase 3 trial TRAIN-2 included 438 patients from 37 Dutch hospitals.
- Patients were randomly assigned (1:1) to: 3 cycles 5-fluoruoracil, epirubicin-cyclophosphamide-trastuzumab (FEC-T) + pertuzumab (Ptz), followed by 6 cycles paclitaxel-trastuzumab-carboplatin (PTC) + Ptz or to 9 cycles PTC + Ptz.
- Primary endpoint: pathological complete response (pCR; previously reported: 67% with vs 68% without anthracyclines, p=0.95)
- Secondary efficacy endpoints (intention-to-treat population): event-free survival (EFS), overall survival (OS), disease-free survival (DFS).
- Adverse events (grade 3 or higher) were reported.
- Funding: Roche.
- Three-year EFS was 93.5% without and 92.7% with anthracyclines, with no benefits observed with anthracyclines in any of the subgroups (HR status, age, size, nodal status, grade).
- Three-year OS was 98.2% without vs 97.7% with anthracyclines (HR not statistically significant).
- Patients who achieved pCR after neoadjuvant treatment showed better DFS (94.1% with pCR vs 85.1% with no pCR, HR 0.42).
- No new safety concerns were found.
- Cardiotoxicity was higher in the anthracycline group and left ventricular ejection fraction decline did not recover to normal during the follow-up in about 1/3 of the patients.
“It’s becoming hard to justify the use of anthracycline-based therapy for HER2+ disease, especially when we have multiple effective targeted treatments,” commented Sara A. Hurvitz, Associate Professor of Medicine, University of California, Los Angeles, Jonsson Comprehensive Cancer Center.