In a Dutch phase II study (TRAIN-3) reported in The Lancet Oncology, Louis et al found that magnetic resonance imaging (MRI)-guided optimization of duration of neoadjuvant chemotherapy was associated with favorable event-free survival in patients with stage II to III HER2-positive breast cancer.
Study Details
In the multicenter trial, 467 patients (235 with hormone receptor [HR]-negative and 232 with HR-positive tumors) were enrolled between April 2019 and May 2021. Patients received neoadjuvant chemotherapy consisting of paclitaxel (80 mg/m², day 1 and 8 of each 21-day cycle), trastuzumab (6 mg/kg on day 1 of each cycle [loading dose 8 mg/kg on day 1 of cycle 1]), carboplatin (AUC = 6 on day 1 of each cycle), and pertuzumab (420 mg on day 1 of each cycle [loading dose 840 mg on day 1 of cycle 1]), for up to 9 cycles; patients were referred to surgery once a complete radiological response was observed on MRI. Patients with a pathological complete response postsurgery completed 1 year of adjuvant trastuzumab and pertuzumab; patients with residual invasive disease continued chemotherapy for a total of 9 cycles followed by 14 cycles of trastuzumab emtansine (3.6 kg/mg, day 1 of each 21-day cycle). The primary endpoint was 3-year event-free survival.
Key Findings
Approximately one-third of patients with HR-negative tumors and one-sixth of those with HR-positive tumors had a pathological complete response after three cycles of chemotherapy.
Median follow-up was 40.1 months (interquartile range = 35.3–45.6 months). Overall, 3-year event-free survival was 92.2% (95% confidence interval [CI] = 88.7%–95.9%) in patients with HR-negative tumors and 92.0% (95% CI = 88.5%–95.6%) in those with HR-positive tumors.
The 3-year event-free survival rates were:
- 96.1% (95% CI = 91.8%–100.0%) in HR-negative patients (n = 91) and 98.6% (95.8%–100.0%) in HR-positive patients (n = 69) receiving one to three cycles
- 89.2% (95% CI = 82.4%–96.6%) in HR-negative (n = 78) and 94.2% (95% CI = 88.8%–99.9%) in HR-positive patients (n = 71) receiving four to six cycles
- 90.6% (95% CI = 83.8%–98.1%) in HR-negative (n = 66) and 85.4% (95% CI = 78.3%–93.1%) in HR-positive patients (n = 92) receiving seven to nine cycles.
Grade 3 and 4 adverse events occurred in 52% and 6% of patients, respectively, receiving one to three cycles; 66% and 10% of those receiving four to six cycles, and 72% and 13% of those receiving seven to nine cycles. Grade 2 or higher neuropathy occurred in 13%, 35%, and 51% of patients, respectively. No treatment-related deaths were observed.
The investigators concluded: “MRI-guided optimization of neoadjuvant chemotherapy duration was associated with favorable 3-year event-free survival outcomes in patients with stage II–III HER2-positive breast cancer. This approach represents a novel strategy that reduces treatment burden, minimizes toxicity, and preserves quality of life in a subset of patients with early HER2-positive breast cancer.”
Gabe S. Sonke, MD, of the Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, is the corresponding author for The Lancet Oncology article.
DISCLOSURE: The study was funded by Roche Netherlands. For full disclosures of the study authors, visit thelancet.com.
