In a Dutch phase II study (TRAIN-3) reported in The Lancet Oncology, Anna van der Voort, MD, and colleagues found that magnetic resonance imaging (MRI) detected complete radiologic response after only three cycles of neoadjuvant chemotherapy in many patients with stage II to III HER2-positive breast cancer.
Anna van der Voort, MD
Study Details
In the multicenter trial, 467 patients were enrolled between April 2019 and May 2021, including 235 with hormone receptor (HR)-negative disease and 232 with HR-positive disease. Patients received neoadjuvant chemotherapy consisting of up to nine 21-day cycles of:
- Paclitaxel at 80 mg/m² on days 1 and 8 of each cycle
- Trastuzumab at a loading dose 8 mg/kg on day 1 of cycle 1, followed by 6 mg/kg on day 1 in all subsequent cycles
- Carboplatin at AUC 6 mg/mL per min on day 1 of each 3-week cycle
- Pertuzumab at a loading dose of 840 mg on day 1 of cycle 1 and then at 420 mg on day 1 of each subsequent cycle.
Response to treatment was monitored by breast MRI every three cycles. Patients underwent surgery when a complete radiologic response was observed or after completing nine therapeutic cycles; surgery was performed within 6 weeks after last receipt of chemotherapy.
The primary endpoint of the trial is 3-year event-free survival; results are to be presented in a future report. In the current analysis, the primary outcome measures were radiologic complete response and pathologic complete response according to HR-negative and HR-positive disease status.
Key Findings
Median follow-up was 26.4 months among patients with HR-negative disease and 31.6 months among those with HR-positive disease. Among 233 evaluable patients with HR-negative disease, radiologic complete response was observed in 84 (36%, 95% confidence interval [CI] = 30%–43%) after one to three cycles of chemotherapy, 140 (60%) after one to six cycles, and 169 (73%) after one to nine cycles. Among 232 evaluable patients with HR-positive disease, radiologic complete response was observed in 68 (29%, 95% CI = 24%–36%) after one to three cycles, 118 (51%) after one to six cycles, and 138 (59%) after one to nine cycles.
Among 169 patients with HR-negative disease with a radiologic complete response after one to nine cycles, pathologic complete response was observed in 147 (87%), including in 74 (88%) of 84 after one to three cycles and 124 (89%) of 140 after one to six cycles. Among 138 patients with HR-positive disease with radiologic complete response after one to nine cycles, pathologic complete response was observed in 73 (53%), including 34 (50%) of 68 after one to three cycles and 63 (53%) of 118 after one to six cycles.
Grade 3 or 4 adverse events occurred in 69 (43%) of 160 patients who received one to three cycles, 109 (74%) of 147 patients who received four to six cycles, and 129 (81%) of 160 patients who received seven to nine cycles. No treatment-related deaths were reported.
The investigators concluded, “In our study, a third of patients with stage II to III HR-negative and HER2-positive breast cancer had a complete pathological response after only three cycles of neoadjuvant systemic therapy. A complete response on breast MRI could help identify early complete responders in patients who had HR-negative tumors. An imaging-based strategy might limit the duration of chemotherapy in these patients, reduce side effects, and maintain quality of life if confirmed by the analysis of the 3-year event-free survival primary endpoint. Better monitoring tools are needed for patients with HR-positive and 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.
