Time for Standard Alert-Based PRO Monitoring in BC

SAN ANTONIO — Weekly patient-reported outcomes monitoring combined with an automated alert system improved fatigue and overall quality of life and prolonged survival in patients with advanced breast cancer, according to the results of the PRO-B study. 

The study demonstrated that “implementing alert-based [patient-reported outcome] monitoring in routine care settings across a wide range of providers and different settings can be successfully done,” reported lead investigator Maria Karsten, MD, with Charité – Universitätsmedizin Berlin in Berlin, Germany, in an oral presentation at the San Antonio Breast Cancer Symposium (SABCS) 2024.

Monitoring of patient-reported outcomes “should become standard of care for advanced breast cancer patients,” the researchers wrote in their SABCS abstract.

A growing body of evidence indicates that monitoring patient-reported outcomes helps patients track their symptoms during their medical treatment, improves adherence to oral cancer therapeutics, reduces unplanned emergency room and hospital admission, and even prolongs survival, all while enhancing communication between patients and the care team, Karsten told attendees. 

Yet, uptake in clinical cancer care “has not been as fast as one would think,” she said. “This was the rationale behind designing the PRO-B trial.”

This multicenter, superiority, randomized controlled trial enrolled 909 patients with metastatic breast cancer from 52 breast centers across Germany. Patients had a life expectancy of more than 3 months, were under active treatment, and had access to a mobile device. Patients were randomized according to localization of metastases, histological subtype of tumor, and type of study center.

The 456 patients in the intervention group received weekly outcome questionnaires on their personal smartphone that allowed them to report their symptoms. These questionnaires were linked to an automatic alert system. In the case of deteriorating scores, an alert was automatically sent to the care team, which then contacted the patient within 48 hours to ask about their status and allow the care team to take action, if needed. 

In contrast, the 453 patients in the control group received outcome questionnaires every 3 months, but their answers were not connected to the alert system.

The two groups were well balanced in clinical characteristics. More than half of patients in each group had multiple metastatic locations and/or brain metastases, and close to half were on chemotherapy while in the trial.

Response rates of the questionnaires were high — 92% at 3 months, 89% at 9 months, and 90% at 12 months in the intervention group, and 77%, 70% and 72%, respectively, in the control group. The median follow-up duration was 64 weeks for the intervention group and 52 weeks for the control group.

The primary outcome was fatigue T-score at 6 months, with higher scores indicating greater fatigue. At the baseline, patients in the intervention group had a score of 57.6, which dropped to 53.6 at 6 months, with the benefit continuing at 9 and 12 months (52.3 at 9 months and 53.9 at 12 months).

In contrast, the fatigue T-score at baseline was 60.2 in the control group and did not improve significantly over the study period (58.7 at 6 months and 59.2 at 9 and 12 months). 

Alert-based monitoring of patient-reported outcomes not only provided a “statistically significant” reduction in fatigue at 6 months but also a “clinically meaningful” reduction of fatigue, with a minimum clinically important difference of −3.3 in the T-score metric, Karsten noted.

There was also an overall survival benefit with alert-based monitoring, with a 29% reduction in mortality in the intervention group compared with the control group (hazard ratio [HR], 0.71). This effect was even more pronounced in patients with visceral metastases (HR, 0.51) and triple-negative disease (HR, 0.61).

Notably, said Karsten, a “very clear picture emerged” when the team took a closer look at the alert rate and symptom burden of those patients who died during the study.

Starting 3-6 months before death, the alert rate steadily increased, reaching a peak in the last month before death. “This picture is also seen in the symptom burden that those patients who died had to go through at the end of life,” Karsten said. 

Not Yet Standard of Care

Karsten shared some comments from participants in the intervention group. 

“This study has done me a lot of good. I received precise support when I was feeling bad. It’s a shame it’s over,” one participant said. Another said she “felt protected.”

Discussant for the study, Gabrielle Rocque, MD, MSPH, wonders why this alert-based monitoring is not yet standard in oncology, given that multiple studies going back to 2015 have shown a benefit. 

“We now have 9 years of data across multiple different countries to say that this could be done. I think this really begs the question — why are we not using remote symptom monitoring for all patients with metastatic breast cancer that are on active treatment?” said Rocque, with University of Alabama at Birmingham O’Neal Comprehensive Cancer Center.

There is some “clear movement” in this direction, Rocque noted, with more oncology practices implementing patient-reported outcome systems.

From a policy standpoint, the Center for Medicare and Medicaid Enhancing Oncology Model will require practices to use electronic patient-reported outcome systems for participants, she noted.

For practices looking to implement a patient-outcome reporting system, Rocque recommends checking out the Proteus Consortium website for guidance and help.

The PRO-B study had no commercial funding. Karsten consults for Pfizer, AstraZeneca, Roche and Gilead. Rocque consults for Gilead, Armada, and Pfizer.