Highlight
• Electronic patient-reported outcomes combined with vital sign monitoring may maintain or improve quality of life (QOL) in patients with ERBB2-positive metastatic breast cancer receiving trastuzumab deruxtecan (T-DXd).
• The PRO-DUCE randomized clinical trial showed meaningful improvements in role, cognitive, and social functioning, and reduced fatigue in the monitoring group.
• Survival outcomes were similar between the intervention and usual care groups, highlighting the value of symptom management for supportive care rather than survival benefit.
• This remote monitoring approach facilitates early symptom detection and responsive medical staff alerting, potentially optimizing patient-centered oncology care.
Study Background and Disease Burden
Metastatic breast cancer (MBC) characterized by ERBB2 (formerly HER2)-positivity represents a substantial clinical challenge due to its aggressive clinical course and systemic disease spread. Trastuzumab deruxtecan (T-DXd), an antibody-drug conjugate targeting the ERBB2 receptor, has emerged as a novel and highly effective treatment option that has transformed standard care paradigms. Despite superior efficacy, T-DXd treatment can be associated with specific adverse events—including fatigue, nausea, and interstitial lung disease—that compromise patients’ quality of life (QOL) and functional status.
As patient-centered care expands in oncology, incorporating electronic patient-reported outcomes (ePROs) paired with vital sign monitoring may offer a proactive strategy to identify adverse symptoms early, facilitating timely clinical interventions to mitigate symptom burden. Such approaches are particularly relevant given the symptom complexity and potential toxicity associated with T-DXd.
Study Design
The PRO-DUCE trial is a multicenter, randomized clinical trial conducted across 38 Japanese hospitals between March 2021 and December 2024. It enrolled 111 female patients with ERBB2-positive MBC who were deemed eligible for T-DXd therapy. Participants were randomized 1:1 into either a monitoring group or a usual care group.
In the monitoring arm, patients utilized smartphones or tablets to submit weekly symptom reports electronically and recorded daily vital signs including body temperature and percutaneous oxygen saturation. Real-time alerts were generated and sent to medical staff when preset thresholds for symptoms or vital signs were exceeded, prompting clinical review.
The usual care group received routine clinical management without this additional digital monitoring.
The primary endpoint was the change in global health status score at 24 weeks from baseline, measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). Secondary endpoints comprised changes in functional and symptom subscales as well as survival outcomes.
Key Findings
Among 111 enrolled patients (mean age 57.1 years), baseline characteristics and QOL scores were comparable between study arms. At 24 weeks, the monitoring group demonstrated a higher mean change from baseline in the global health status score by 8.0 points (90% CI, 0.2 to 15.8), indicating a favorable trend toward improved overall QOL compared to usual care; the difference approached but did not reach conventional statistical significance (P = .09).
Significant improvements were observed in several functional domains for the monitoring group: role functioning improved by 10.0 points (95% CI, 1.1 to 18.9), cognitive functioning by 6.3 points (95% CI, 1.1 to 11.5), and social functioning by 10.9 points (95% CI, 3.9 to 18.0). These domains are crucial aspects of daily life and social engagement, underscoring the clinical relevance of the intervention.
Regarding symptom burden, fatigue scores were significantly lower in the monitoring group (mean difference, -8.4; 95% CI, -16.1 to -0.6), reflecting reduced patient-experienced fatigue. No substantial differences were observed for nausea or vomiting symptoms. Importantly, no survival benefit was identified between groups during the study period, suggesting the intervention primarily influences quality rather than quantity of life.
Expert Commentary
The PRO-DUCE trial highlights the potential of integrating ePROs and vital sign monitoring into oncology care for patients receiving modern targeted therapies like T-DXd. By enabling early detection of symptom changes and physiological deviations, this strategy can empower clinicians to intervene promptly, possibly preventing QOL deterioration and functional decline.
While the study did not meet the primary endpoint with conventional statistical significance, the observed effect sizes in several functional domains and fatigue are clinically meaningful and consistent with the hypothesis that enhanced monitoring supports patient-centered care. The lack of survival difference is expected given the intervention focuses on supportive management rather than anticancer efficacy.
Limitations include the relatively small sample size and the open-label design, which may influence patient self-reporting. Furthermore, the trial was conducted within a homogeneous Japanese population, which may restrict generalizability to other ethnic groups or healthcare systems. Future research should explore the scalability of digital monitoring tools and investigate direct impacts on healthcare utilization and cost-effectiveness.
Conclusion
The PRO-DUCE multicenter randomized trial demonstrates that electronic symptom tracking combined with vital sign monitoring in patients with ERBB2-positive metastatic breast cancer undergoing trastuzumab deruxtecan therapy may preserve or improve quality of life, particularly in functional domains and fatigue reduction. Although survival remains unaffected, this approach represents a promising adjunct to enhance comprehensive patient management and facilitate timely clinical responses to toxicity.
Implementation of digital health tools like ePROs could become integral for delivering personalized, proactive oncology care, ultimately fostering better patient experiences during complex anticancer treatments. However, further validation across diverse populations and healthcare settings is warranted to optimize and standardize these emerging monitoring paradigms.
References
1. Kikawa Y, Uemura Y, Taira T, et al. Electronic Patient-Reported Outcomes With Vital Sign Monitoring During Trastuzumab Deruxtecan Therapy: The PRO-DUCE Randomized Clinical Trial. JAMA Netw Open. 2025 Aug 1;8(8):e2527403. doi:10.1001/jamanetworkopen.2025.27403.
2. Modi S, Park H, Murthy RK, et al. Antitumor Activity and Safety of Trastuzumab Deruxtecan in Patients With HER2-Low-Expressing Advanced Breast Cancer: Results From a Phase Ib Study. J Clin Oncol. 2020;38(17):1887-1896. doi:10.1200/JCO.19.02724.
3. Basch E, Deal AM, Dueck AC, et al. Overall Survival Results of a Trial Assessing Patient-Reported Outcomes for Symptom Monitoring During Routine Cancer Treatment. JAMA. 2017 Jul 18;318(2):197-198. doi:10.1001/jama.2017.7156.