By: M. Alexander Otto, PA, MMSc
From: medscape.com
MRI can identify patients with HER2-positive breast cancer who don’t need a full course of neoadjuvant chemotherapy, letting them avoid the toxicity of unnecessary treatment while preserving 3-year event-free survival, new trial findings suggest.
The study, published in The Lancet Oncology, found that patients had “excellent” outcomes even if they received only 1-3 preoperative chemotherapy cycles based on MRI results.
However, some experts cautioned that it’s too soon to integrate MRI-guided chemotherapy duration into practice.
Previous studies have found that some patients show an early pathological complete response after just a few neoadjuvant chemotherapy cycles instead of the usual 6 or more, but there hasn’t been a reliable way to know when shorter treatment is enough.
In the TRAIN-3 trial, Dutch investigators tested preoperative MRI as a guide.
After every 3 cycles, patients had an MRI scan; those with a complete radiological response went straight to surgery, whereas those without a complete response continued chemotherapy for up to 9 cycles.
Overall, patients were about evenly split in terms of chemotherapy duration, with roughly one third each receiving 1-3, 4-6, or 7-9 cycles.
After surgery, patients who had a pathological complete response received 1 year of adjuvant trastuzumab and pertuzumab. Those with residual invasive cancer continued chemotherapy for a total of 9 cycles, followed by 14 cycles of trastuzumab emtansine.
The approach seemed to work. Among patients who underwent surgery after 1-3 chemotherapy cycles, event-free survival at 3 years was 96.1% for those with HR-negative tumors and 98.6% for those with HR-positive tumors.
Patients who went to surgery after 4-6 cycles had 3-year event-free survival rates of 89.2% in HR-negative and 94.2% in HR-positive disease, whereas those who received 7-9 cycles had rates of 90.6% and 85.4%, respectively.
Those outcomes were in line with previously reported 3-year event-free survival rates in this patient population.
As for treatment toxicity, patients who received fewer chemotherapy cycles had lower rates of grade 3-4 adverse events. They were also less likely to report a clinically significant deterioration in health-related quality of life than those who received 7-9 cycles.
“These findings support a therapeutic strategy that could substantially reduce treatment burden while maintaining clinical efficacy in well-selected patients,” wrote the researchers, led by Gabe Sonke, MD, PhD, the Netherlands Cancer Institute, Amsterdam, Netherlands.
However, MRI wasn’t perfect at predicting surgical outcomes. It performed well in patients with HR-negative disease, correctly predicting pathologic complete response 87% of the time, but in those with HR-positive disease, clearance on MRI correctly predicted pathological complete response in only 53% of patients.
As a result, some patients still had residual disease after MRI clearance, particularly those with HR-positive tumors.
That’s likely because HR-positive disease appears more diffuse and less well defined on MRI, making it harder to determine whether tumors are truly gone, Sonke told Medscape Medical News.
In addition, there more pathological complete responses in the HR-negative group, which lowered the probability of false‑negative MRI scans.
The investigators didn’t detail how patients with residual disease after MRI clearance fared but noted that early surgery didn’t lead to worse survival. At the same time, they emphasized the need for longer follow-up, especially in patients with HR-positive disease because of late recurrence risk.
Going forward, the researchers said, incorporating biomarkers might boost the predictive accuracy of MRI in the neoadjuvant setting.
Two editorialists agreed.
TRAIN-3 showed that response-adapted neoadjuvant treatment “is feasible, preserves excellent long-term outcomes, and reduces toxicity in patients who have an early response,” wrote Guilherme Nader-Marta, MD, and Erica L. Mayer, MD, both of the Dana-Farber Cancer Institute, Boston.
However, they stressed, the trial also underscored the limitations of imaging alone, pointing to the need for complimentary biomarkers.
Sonke said the Dutch team is currently analyzing circulating tumor DNA clearance in TRAIN-3 to see if it improves MRI-based prediction of surgical clearance. Positron emission tomography also holds promise.
In the meantime, Sonke said, some hospitals in the Netherlands have already adopted the TRAIN-3 approach specifically for patients with HR-negative disease, and guidelines there are being updated.
Kathy Miller, MD, medical breast cancer specialist at Indiana University, Indianapolis, had a cautious take. She told Medscape Medical News the trial findings are “interesting but not ready to inform practice.”
“There have been prior attempts to use MRI to identify patients who have a [pathological complete response], to either attenuate therapy or support trials that would eliminate surgery,” Miller noted.
But, she said, the proportion of patients who have residual disease despite MRI clearance “is too high to support either effort.”
Barbara Jacoby is an award winning blogger that has contributed her writings to multiple online publications that have touched readers worldwide.