Abstract OT1-12-08: Randomized study comparing electronic patient reported outcomes (ePROs) monitoring with routine follow up during trastuzumab deruxtecan treatment in patients with inoperable or metastatic breast cancer (PRO-DUCE study)
Authors: Sangai Takafumi , Kikawa Yuichiro , Hosoda Mitsuchika , Hamanaka Yohei , Tanabe Yuko , Yoshida Tatsuya , Tane Kaori , Takabatake Daisuke , Taira Tetsuhiko , Araki Kazuhiro , Iwamoto Takayuki , Takada Mamoru , Narui Kazutaka , Yamaguchi Takeshi , Yamada Akimitsu , Miura Tomoko , Uemura Yukari , Aihara Tomohiko , Mukai Hirofumi , Taira Naruto 
Published: March 2022

Abstract
Background: Trastuzumab Deruxtecan (T-DXd) is a novel antibody-drug conjugate that targets human epidermal growth factor receptor 2 (HER2) with a DNA topoisomerase I inhibitor payload and has demonstrated antitumor activity in clinical trials. Based on the results of a global Phase II clinical trial (DESTINY-Breast01, NCT03248492), T-DXd was conditionally approved for the treatment of patients with HER2+ unresectable or metastatic breast cancer who had received ≥2 prior anti-HER2 based therapies (US, EU, UK, etc) or after prior chemotherapy (Japan). With regards to the safety profile, the incidence of cumulative toxicities such as peripheral neuropathy and edema was lower with T-DXd as compared to what has been observed with taxanes. However, chemotherapy-induced nausea and vomiting (CINV), fatigue, and neutrophil count decrease were observed as treatment emergent adverse events (TEAE). Interstitial lung disease (ILD)/pneumonitis was especially observed in 15.2% of patients treated with T-DXd, leading to death in 2.7% of patients. These adverse events need appropriate monitoring and management in daily clinical practice. We hypothesized that electronic patient-reported outcomes (ePROs) monitoring would allow early detection of adverse events due to T-DXd and thus improve patient safety and quality of life (QoL). Study design: This is an open-label, multicenter, randomized controlled study comparing ePRO monitoring with routine follow-up of patients with HER2+ advanced or metastatic breast cancer who receive T-DXd in routine clinical practice. Patients randomized to the ePRO group are monitored through weekly PRO-CTCAE assessment as well as daily temperature and SpO2 measurement using the ePRO application on the patient's mobile device. Changes in symptoms are monitored by the attending physician using an electronic chart. In addition, an e-mail alert is sent to the site medical staff if any symptoms exceed a predetermined threshold. The primary endpoint of the study is the change from baseline in the EORTC QLQ-C30 (Global QoL) score at 24 weeks. Secondary endpoints include time to deterioration of Global QoL, EORTC FA12 score change, overall survival, progression-free survival, and adherence to the ePRO monitoring as assessed by the proportion of patients completing the questionnaires. Analysis of primary endpoint will be done using mixed effects models for repeated measures (MMRM) and sample size will be estimated based on the Wald test for differences between groups in mean parameters at 24 weeks. To detect 10-points score difference between the groups with a standard deviation of 24, with a two-sided alpha level of 10%, and a power of 87%, 55 patients would be required in each group. Enrollment started in March 2021. Clinical trial identification: jRCTs031200387
Citation Format: Takafumi Sangai, Yuichiro Kikawa, Mitsuchika Hosoda, Yohei Hamanaka, Yuko Tanabe, Tatsuya Yoshida, Kaori Tane, Daisuke Takabatake, Tetsuhiko Taira, Kazuhiro Araki, Takayuki Iwamoto, Mamoru Takada, Kazutaka Narui, Takeshi Yamaguchi, Akimitsu Yamada, Tomoko Miura, Yukari Uemura, Tomohiko Aihara, Hirofumi Mukai, Naruto Taira. Randomized study comparing electronic patient reported outcomes (ePROs) monitoring with routine follow up during trastuzumab deruxtecan treatment in patients with inoperable or metastatic breast cancer (PRO-DUCE study) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT1-12-08.