Alert-Based ePRO Monitoring Reduces Fatigue in Metastatic Breast Cancer

According to results from the multicenter PRO B trial (German Clinical Trials Register: DRKS00024015), published in JAMA Oncology, weekly electronic patient-reported outcome (ePRO) monitoring with alert-based clinical response reduced fatigue and improved physical functioning compared with usual care in patients with metastatic breast cancer.¹ At 6 months, adjusted mean fatigue was 54.5 (95% CI, 53.7-55.4) in the intervention group vs 59.9 (95% CI, 59.0-60.8) with usual care, a mean difference of −5.4 points (95% CI, −6.6 to −4.1; P <.001) that exceeded the prespecified minimal clinically important difference (MCID) of 3.3 points.

The open-label trial randomly assigned 924 women with metastatic breast cacner across 52 breast cancer centers in Germany to weekly ePRO monitoring via a smartphone application, with automated alerts for clinically meaningful deterioration routed to trained nurses or physicians who contacted patients by telephone within 48 hours, or to usual care with quarterly PRO questionnaires and no alerts. Among the 909 patients included in the primary analysis, physical functioning was also significantly higher with ePRO monitoring at 6 months (mean difference, 4.0; 95% CI, 2.6-5.4), exceeding its MCID of 3.2 points. The between-group difference in quality of life was 0.8 points (95% CI, 0.02-1.5), below the 2.9-point MCID.

"The new medications often no longer need to be administered at the hospital but can be taken at home. As a result, we see patients less frequently, and our medical oversight has become somewhat incomplete. In order to close this gap, we developed the PRO B digital treatment concept,” said Maria M. Karsten, Dr habil, senior attending physician at the Charité Breast Cancer Center and PRO B trial investigator, in a news release.²

Study Design

PRO B was an investigator-initiated, open-label, superiority randomized clinical trial conducted from May 2021 to June 2023 across 52 academic and community breast cancer centers in Germany.1 Eligible patients were 18 years or older with metastatic breast cancer receiving systemic therapy, a life expectancy longer than 3 months, an ECOG performance status of 0 to 2, and smartphone access. Patients were randomly assigned 1:1, stratified by metastatic site distribution, hormone receptor/HER2 subtype, and study center. The intervention group completed weekly PRO questionnaires using EORTC computerized adaptive testing core items, with alerts triggered by clinically meaningful deterioration or worsening on a single health transition item; alert criteria were revised in September 2022 to increase sensitivity. The control group completed the full questionnaire quarterly with no alerts and no PRO visibility to the care team.

Of 2008 patients screened, 924 (46.0%) were randomized and 909 (45.3%) were included in the primary modified intent-to-treat analysis (median age, 50 years; range, 19-83). The primary end point, changed early in the trial from 12-month to 6-month fatigue because of anticipated attrition, was assessed using a linear mixed-effects model adjusting for baseline fatigue, stratification factors, and enrollment period.

"During these phone calls, we discuss whether medication dosages should be adjusted or offer practical tips for managing symptoms. But we also detect serious adverse effects more quickly—such as those indicated by a seemingly harmless symptom like fatigue—and can immediately schedule the patient for a hospital appointment,” added Karsten.²

Secondary and Exploratory Outcomes

In the intervention group, 24,180 follow-up PRO assessments were completed, generating 3019 alerts (12.5%; median of 5 per patient); 2559 led to patient contact, 85.7% within 48 hours.1 In a claims data subpopulation of 235 patients (25.9%), hospitalization and emergency department visit rates at 12 months were lower with ePRO monitoring (incidence rate ratio, 0.52; 95% CI, 0.45-0.78; and 0.76; 95% CI, 0.63-0.92, respectively). In an exploratory analysis of the full cohort, 12-month overall survival (OS) was 87.6% with ePRO monitoring vs 84.7% with usual care (adjusted HR, 0.72; 95% CI, 0.52-0.99); among patients with hormone receptor–positive, HER2-negative disease, 12-month OS was 88.5% vs 82.7% (adjusted HR, 0.69; 95% CI, 0.47-1.00). Time to first change in systemic therapy did not differ between groups (adjusted HR, 0.89; 95% CI, 0.74-1.08), suggesting the benefit was not driven by earlier treatment switching.¹

Clinical Context and Limitations

The authors cautioned that results should be interpreted with care. Baseline PRO assessments were collected after randomization rather than before, questionnaire completion and follow-up retention were higher in the intervention group, and the trial was not blinded—features that could have amplified between-group differences, particularly at later time points. Only patients with smartphone access and German language proficiency were eligible, limiting generalizability. Health care utilization data were available for only about one-quarter of the cohort, and survival findings were exploratory, underpowered, and based on site-reported follow-up without registry linkage, so they should not be considered confirmatory. The authors noted that the intervention did not appear to work by prompting earlier treatment changes, and instead may have improved outcomes through earlier clinical contact, supportive care, or enhanced patient-clinician communication.

REFERENCES

1. Karsten MM, Gebert P, Pross T, et al. Electronic patient-reported outcome monitoring with alert-based interventions in metastatic breast cancer: a randomized clinical trial. JAMA Oncol. Published online August 6, 2026. doi:10.1001/jamaoncol.2026.2661

2. Close digital support helps women with breast cancer. News release. Charité – Universitätsmedizin Berlin. August 6, 2026. Accessed August 14, 2026. https://tinyurl.com/5acsy2n3