Alert-based patient-reported outcome monitoring improves breast cancer symptom control
Key takeaways:
- Patients assigned the intervention had less fatigue and improved quality of life.
- They also exhibited a 29% reduced risk for death.
SAN ANTONIO — Use of alerts triggered by patient-reported outcome monitoring improved symptom control for patients with advanced breast cancer, according to results of the randomized PRO B trial.
The approach conferred a clinically meaningful reduction in fatigue, improved quality of life and led to better physical functioning, findings presented at San Antonio Breast Cancer Symposium showed.
Researchers also observed a 29% reduction in mortality among patients assigned the intervention.
“Based on these findings, [patient-reported outcome] monitoring should become standard of care for [patients with] advanced breast cancer,” Maria Margarete Karsten, MD, managing senior physician at the Breast Center of Charité-Universitätsmedizin Berlin in Germany, said during a presentation.
Benefits of PROs
Up to about one-third of people with breast cancer develop distant metastases. Development of metastatic disease shifts the treatment focus from cure to extending survival and ensuring quality of life. Prior research suggests patient-reported outcomes (PROs) may help achieve both, Karsten said.
“There is increasing evidence in clinical medicine that the use of PROs supports patients through symptom monitoring during treatment, improves adherence to oral cancer therapeutics [and] reduces unplanned emergency room and hospital admissions,” Karsten said.
PROs also can improve clinician-patient communication, she added.
The randomized, multicenter PRO B study evaluated the effect of weekly electronic PRO monitoring in combination with an automated alert system as part of routine care for people with advanced breast cancer.
Investigators enrolled 924 patients treated at 52 certified breast centers in Germany between May 2021 and June 2023. All patients had metastatic disease, a life expectancy of more than 3 months, and access to a smartphone or other mobile device.
Researchers randomly assigned 463 patients to an intervention group. They received a weekly questionnaire via their mobile device that included selected items from EORTC QLQ-C30, a validated instrument that assesses quality of life among people with cancer.
When PRO values declined based on a comparison of scores from 1 and 4 weeks prior, the treating center received an automated alert, contacted the patient within 48 hours to ask about the reported symptoms, determined whether intervention was necessary and documented any action taken.
Researchers assigned the other 461 patients to a control group. They received PRO questionnaires every 3 months via their mobile device but were not part of the alert system.
The intervention and control groups appeared balanced with regard to age (mean, 51 years in both), breast cancer subtype (hormone receptor positive, 80.3% vs. 79.5%), presence of brain or multiple metastases (55.5% vs. 55.2%), proportion with ECOG performance status of 0 to 2 (94.4% vs. 95%) and therapy at randomization (endocrine therapy, 60.1% vs. 57.8%; chemotherapy, 48.9% vs. 48.3%; anti-HER2, 22.1% vs. 23.8%).
Patient-reported fatigue at 6 months after randomization served as the primary endpoint. Secondary endpoints included survival at 12 months, survival among people with triple-negative breast cancer, survival among those with visceral metastasis and a health economic evaluation.
Investigators used linear mixed models adjusted for baseline PROs and other confounders to compare PRO values.
‘Clear picture’ emerges
After excluding patients who did not respond to any questionnaires, the intervention group included 456 patients at baseline, 399 (88%) at 6 months and 278 (61%) at 12 months. The control group included 453 people at baseline, 362 (80%) at 6 months and 243 (54%) at 12 months.
Median follow-up was 64 weeks (interquartile range, 37-100) in the intervention group and 52 weeks (interquartile range, 26-91) in the control group.
An analysis of people remaining on the study at various time points showed consistently higher response rates in the intervention group at 3 months (92% vs. 77%), 6 months (89% vs. 72%), 9 months (89% vs. 70%) and 12 months (90% vs. 72%).
PRO responses in the intervention group triggered an average of about 12 automated alerts per week.
The study met its primary endpoint, showing a significant reduction in fatigue T score at 6 months in the intervention group compared with the control group (53.2 vs. 58.7). The difference persisted at 9 months (52.3 vs. 59.2) and 12 months (53.9 vs. 59.2).
The benefit of the intervention appeared more pronounced among patients with visceral metastases, as well as those with hormone receptor-negative disease.
“We not only had a statistically significant reduction in fatigue, [but] we also had a clinically meaningful reduction, with a [minimal clinically important difference (MCID)] of –3.3 in the T score metric,” Karsten said. “This is equivalent of 8 points in the EORTC QLQ-C30 metric, which is considered clinically meaningful by the EORTC working group.”
Results also showed a survival benefit with the intervention in the overall study population (adjusted HR = 0.71; 95% CI, 0.51-0.99). The survival benefit appeared more pronounced in the subgroup of patients with visceral metastases (adjusted HR = 0.51; 95% CI, 0.13-2), but it did not reach statistical significance due to the small sample size, Karsten said.
“In light of these findings, we took a closer look at the symptom burden and alert rate of those patients who unfortunately died while on the PRO B study, and a very clear picture emerged,” Karsten said.
The alert rate increased steadily beginning 3 to 6 months prior to death, and it increased up to 50% in the last month before death, Karsten said.
“This stands in contrast to the steady alert rate for patients who were still alive at the end of the PRO B study,” she said.
Results also showed a steady increase in symptom burden among patients who neared death, with a higher rate of symptoms in the control group than the intervention group.
“[The PRO B findings show] implementing alert-based PRO monitoring in routine care across a wide range of providers and in different settings can be successfully done,” Karsten said.
References:
- Basch E, et al. JCO Clin Cancer Inform. 2023;doi:10.1200/CCI.22.00187.
- Basch E, et al. J Clin Oncol. 2016;doi:10.1200/JCO.2015.63.0830.
- The PROTEUS Consortium. https://theproteusconsortium.org/. Accessed April 1, 2025.
Perspective
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These investigators aimed to determine if a remote symptom monitoring program using electronic patient-reported outcomes improves fatigue among patients with metastatic breast cancer. This is an incredibly patient-centric question.
Seventy percent of people in the study population had visceral disease and approximately half were on chemotherapy. Eighteen percent of people died within the study period, so this population is somewhat enriched for patients who had a higher symptom burden and were potentially approaching the end of life.
This study shows remote symptom monitoring using electronic PROs is effective for women with metastatic breast cancer, with the greatest impact in populations traditionally considered to have high morbidity and mortality.
Results showed a significant reduction in fatigue at 6 months — the study’s primary outcome. It’s important to note the greatest differences were among patients who had visceral disease, as well as brain metastases or multiple sites of disease, rather than those who might have had a more indolent course. In the last month of life, approximately half of patients’ symptoms triggered an alert for something that required attention by the clinical team, compared with a rate of 10% to 15% for those not at the end of life.
There are some limitations. The fact this was a heterogenous population makes it a little hard to interpret which patients may have benefitted the most from this intervention. This also requires a smartphone app, so there may be limited applicability to populations with low digital literacy.
It’s been 9 years since the original publication by Basch and colleagues that looked at remote symptom monitoring using electronic PROs for people with advanced cancer. Their results demonstrated an improvement in quality of life, as well as symptom control, time on chemotherapy and survival.
I think this begs the question: Why are we not using remote symptom monitoring for all patients with breast cancer on active treatment? We now have 9 years of data from multiple countries showing this can be done. There also has been clear movement in this direction from a policy standpoint, as the CMS Enhancing Oncology Model requires the use of electronic PROs for participants.
As we think about where we go from here, there are a lot of available data related to how to think about implementation in clinical practice. One paper examined the tenets for implementing electronic PROs for remote symptom monitoring during cancer treatment. The PROTEUS Consortium website also is a really wonderful resource for PROs, both within clinical trials and standard care in oncology.
There is no doubt in my mind that remote symptom monitoring using electronic PROs benefits patients and that implementation at scale is possible.
I think it’s time to think about the next generation of questions we should be asking regarding use of electronic PROs.
Is there an opportunity to customize our electronic PRO tools, potentially using AI to guide who should get what surveys and when? I often wonder what the role of electronic PROs is based on different patient profiles. Should it look different for a patient with a lower symptom burden or someone just starting first-line therapy with a CDK 4/6 inhibitor for ER-positive disease than it does for someone who is on more aggressive chemotherapy or potentially approaching end of life?
How long should we continue surveys? Are we going to do weekly surveys for patients who are on the same treatment for the next 5 years? How can we customize it and make this responsive to the needs of patients in the best possible way? And are there differences in the questions we should ask in survivorship or end of life?
There also are real opportunities for us to think about how we identify potentially rare but serious complications through mass collection of electronic PROs and looking at the events that are occurring. Could this replace some of our current post-monitoring approaches that are maybe less patient centric?
Finally, where are the opportunities to include ePROs within clinical trials as more than just outcomes, and as something that we can manage and really improve those symptoms? Could this improve side effect profiles and allow us to keep patients on their medications longer? There are a lot of data to suggest that is the case. It’s time for us to be thinking about some of these questions.
O'Neal Comprehensive Cancer Center
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Karsten MM, et al. Abstract GS1-06. Presented at: San Antonio Breast Cancer Symposium; Dec. 10-13, 2024; San Antonio.