Favorable impact of therapy management by an interactive eHealth system on severe adverse events in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer treated by palbociclib and endocrine therapy.

Background: Oral cancer medications offer advantages but also pose challenges for therapy management and adherence. An eHealth-based platform such as CANKADO can help to support therapy management by probing the patient's quality of life (QoL) continuously throughout the course of treatment.

Material and Methods: AGO-B WSG PreCycle (NCT03220178) is a multicenter, randomized phase IV intergroup trial evaluating the impact of eHealth-based Patient-Reported Outcome (ePRO) assessment on QoL in patients with hormone receptor-positive (HR + )/HER2-negative (HER2-) advanced breast cancer treated with palbociclib and endocrine therapy. Patients were randomized (2:1) to CANKADO-active arm (supported by CANKADO PRO-React) or CANKADO-inform arm (drug intake documentation only) This exploratory analysis reports the impact of CANKADO PRO-React on safety. Time to first serious adverse event (SAE) was estimated taking competing risks into account.

Results: While distributions of adverse events (AEs) were similar by arm overall, patients in the CANKADO-active arm had a favorable hazard ratio of 0.67 (95%CI 0.46-0.97; p = 0.04) for time to first SAE and were significantly less likely overall to suffer an SAE than patients in the inform arm. At 24 months, 22.9% [17.9%-27.8%] of patients in CANKADO-active had suffered an SAE vs. 30.3% [22.6%-38.0%] in CANKADO-inform. AE-related dose reductions affected approximately 20% of patients (CANKADO-active: 18.2%, CANKADO-inform: 21.1%).

Conclusion: Exploratory safety analysis of PreCycle demonstrates for the first time in a randomized prospective trial that interactive autonomous eHealth-based support has a substantial favorable impact on the risk of SAEs and mitigates their severity for patients with advanced HR+/HER2- breast cancer on oral tumor therapy.

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [NH reported support for the present manuscript (e.g., funding, provision of study materials, medical writing, article processing charges, etc.) from palleos healthcare; consulting fees from Gilead, Pfizer, Sanofi, Sandoz, Roche, Seagen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, EPG Communication, Lilly, MSD, Pierre Fabre, Roche, Seagen, Viatris, Daiichi Sankyo, Gilead, MEDSCAPE, Novartis, Pfizer, Sanofi, Springer, Zuelligpharma; and co-director position at WSG – West German Study Group. REK reported consulting fees to an immediate family member from Roche/Genentech, Novartis, BMS, Pfizer, Lilly, Sandoz, Daiichi Sankyo, Agendia, AstraZeneca, Merck Sharp & Dohne, Ondonate Therapeutics, Sattle Genetics, and palleos healthcare; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events to an immediate family member from Roche, Novartis, BMS, Amgen, Pfizer, Genomic Health, and NanoString Technologies. TS reported stock or stock options from CANKADO GmbH; other financial or non-financial interests from CANKADO GmbH. RW reported consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events as well as support for attending meetings and/or travel from Agendia, Aristo, BMS, Daiichi Sankyo, Exact Sciences, Glaxo Smith Kline, Lilly, MSD, Mylan, Novartis, Paxman, Pfizer, PINK, Sandoz/Hexal, Riemser, Seattle Genetics/Seagen, Tesaro Bio, Veracyte, Amgen, AstraZeneca, Clovis Oncology, Eisai, Gilead, Hexal, Medstrom Medical, Mundipharma, Nanostring, Ondonate, palleos healthcare, Perre Fabre, PumyBiotechnology, Roche, Sanofi Genzyme, Stemline, Teva, Viatris; other financial or non-financial interests from FOMF, Pomme Med, MCI, Aurikamed, medconcept and Breast Center, Department of Obstetrics and Gynecology and Comprehensive Center (CCC) Munich, LMU University Hospital, Munich Germany. DL reported consulting fees from AstraZeneca, Novartis, Daiichi Sankyo, Amgen, Loreal, High5md, Eli Lilly, Pfizer, Gilead, GSK, Onkowissen; honoraria from Astra Zeneca, Novartis, Daiichi Sankyo, Amgen, Loreal, High5md, Eli Lilly, Pfizer, Gilead, GSK, Onkowissen; payment for expert testimony from AstraZeneca, Novartis, Daiichi Sankyo, Amgen, Loreal, High5md, Eli Lilly, Pfizer, Gilead, GSK, Onkowissen; support for attending meetings and/or travel from AstraZeneca, Novartis, Daiichi Sankyo, Amgen, Loreal, High5md, Eli Lilly, Pfizer, Gilead, GSK, Onkowissen; Board or Advisory Board from AstraZeneca, Novartis, Daiichi Sankyo, Amgen, Loreal, High5md, Eli Lilly, Pfizer, Gilead, GSK, Onkowissen; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from Deutsche Stiftung für junge Erwachsene mit Krebs. OH reported consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events as well as support for attending meetings and/or travel, and participation on a Data Safety Monitoring Board or Advisory Board from Roche, MSD, Gilead, Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Seagen, Amgen, Eisai; from Roche, MSD, Gilead, Novartis, Lilly, Pfizer, AstraZeneca, Daiichi Sankyo, Seagen, Amgen, Eisai. TDecker reported personal fees from Adboards, Novartis and iOMEDICO. MR reported consulting fees from Roche, Daiichi Sankyo, Somatex; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Roche, AstraZeneca, Novartis, Daiichi Sankyo, Gilead, Somatex, Pfizer, Lilly; support for attending meetings and/or travel from Novartis, Pfizer, Gilead and Astra Zeneca. PS reported honoraria from Abbvie, Amgen, AstraZeneca, BMS, MSD Oncology, Pfizer, Merck Serono, Roche, Novartis; consulting or advisory role from Abbvie, Amgen, AstraZeneca, BMS; speakers' bureau from Abbvie, Amgen, AstraZeneca, BMS, Roche, Pfizer; research funding from Abbvie, BMS, Novartis, Roche; travel, accommodations, expenses from Abbvie, AstraZeneca; other from Abbvie, Amgen, BMS, Eisai, Incyte, Ipsen, Gilead Sciences, AstraZeneca, Janssen Oncology, Lilly Medical, Merck Serono, MSD Oncology, Pfizer, Roche, Novartis, Takeda. OG reported consulting fees from Daiichi Sankyo, BMS, Genomic Health/Exact Sciences, Lilly, MSD, Novartis, Pfizer, Roche, Seagen, Pierre Fabre, Gilead, Molecular Health; honoraria from Genomic Health/Exact Sciences, Eisai, Roche, BMS, Pfizer, Novartis, NanoString Technologies, Agendia, AstraZeneca; travel support from Roche, Daiichi Sankyo, all outside of the submitted work; co-director position at West German Study Group (WSG). PAF reported personal fees for advisory board from Agendia, AstraZeneca, Daiichi Sankyo, Eisai, Hexal, Lilly, Merck, Sharp&Dohme, Novartis, Pfizer, Pierre Fabre, Roche, Sanofi Aventis, Seagen; personal fees for invited speaker from AstraZeneca, Daiichi Sankyo, Eisai, Gilead, Lilly, Merck, Sharp&Dohme, Novartis, Seagen; personal fees for medical writing support from Roche; non-financial support to the Institution from BioNTech, Cepheid; non-financial interests: member for Arbeitsgemeinschaft für Gynäkologische Onkologie, ASCO, Deutsche Gesellschaft für Senologie, Translational Research in Oncology. MS reported grants or contracts paid to the Institution from from AstraZeneca, BioNTech, Eisai, German Breast Group, Genentech, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche; consulting fees from AstraZeneca, BioNTech, Eisai, Daiichi Sankyo, Lilly, MSD, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche, Seagen; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca, Novartis, Pfizer, Roche, Seagen; support for attending meetings and/or travel from Pfizer, Roche; patents planned, issued or pending EP 2951317 B1, EP 2390370 B1; participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca, BioNTech, Daiichi Sankyo, Eisai, Lilly, Novartis, Pantarhei Bioscience, Pfizer, Pierre Fabre, Roche and Seagen. All other authors have declared no conflicts of interest.].

(Copyright © 2023. Published by Elsevier Ltd.)