Title of this trial: PRECYCLE: Multicenter, randomized phase IV intergroup trial to evaluate the impact of eHealth-based patient reported outcome (PRO) assessment on quality of life in patients with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer treated with Palbociclib and an aromatase inhibitor- or Palbociclib and Fulvestrant
Abstract # 1008 Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HR+ HER2- metastatic breast cancer patients receiving palbociclib and endocrine therapy: Primary outcome analysis of the multicenter randomized PreCycle trial
Authors: Nadia Harbeck, Peter Fasching, Rachel Wuerstlein, Tom Degenhardt, Diana Lüftner, Ronald Kates, Johannes Schumacher, Philip Raeth, Oliver Hoffmann, Ralf Lorenz, Thomas Decker, Mattea Reinisch, Thomas Göhler, Peter Staib, Oleg Gluz, Timo Schinkoethe, Marcus Schmidt on behalf of the AGO-B WSG PreCycle investigators
Breast cancer is one of the most common types of cancer in women with over 2 million new cases worldwide in 2020 (https://www.iarc.who.int/cancer-type/breast-cancer).
Advanced or metastatic breast cancer (MBC) means that the cancer has spread to other parts of the body and other organs such as bone, liver or lung. MBC is still considered an incurable disease.[i] Living with MBC is a challenge. Treatment goals are prolongation of survival and improvement or maintenance of quality of life (QoL) under therapy by sufficient control of cancer-related symptoms.[ii]
In hormone receptor (HR)-positive, HER2-negative (HR+/HER2-) MBC, CDK4/6 inhibitor-based therapy is now standard of care1, as patient outcome has improved substantially with good QoL across all lines of therapy. CDK4/6 is a protein complex comprises of cyclin-dependent kinases 4 and 6 that serve as a checkpoint in cell division and growth, and its deregulation can induce abnormal cell proliferation and cancer development. Palbociclib is an oral drug and works by targeting the CDK4/6 protein complex in breast cancer cells, causing the cancer to slow or stop growing.
Palbociclib was the first approved CDK4/6 inhibitor worldwide and thus provided a good opportunity to test the benefits of eHealth-based therapy management under oral cancer therapy. First clinical data regarding benefits of eHealth support were generated by remote patient monitoring (RPM) systems supervised by oncologists or trained nurses with regular patient-reported outcome (PRO) documentation.[iii],[iv]
CANKADO (https://cankado.com) is a next-generation, interactive, autonomous eHealth application, and an EU-registered medical device (DE/CA59/BS 392/2021). It works without any intervention by a healthcare professional and can self-detect points in time to initiate symptom questionnaires. The application is available in many languages. The aim of CANKADO is to empower patients, prepare them better for the next contact with the treatment team and initiate this contact when needed due to self-reported symptoms. Patients are queried daily about their general health merely by a smiley slider, graphically based on the EQ visual analogue scale (EQ-VAS).[v] Based on the documented changes in the EQ-VAS value, the software selects the appropriate time to trigger a 14-symptom questionnaire. Once symptoms and their grade of severity are documented, the system recommends to the patient whether and how urgently the treatment center should be contacted. In contrast to an RPM system, healthcare professionals are not involved at any time point until the patient contacts the center.
In the PreCycle randomized, phase IV clinical trial, researchers investigated the impact of a next-generation, interactive, autonomous eHealth application on patient QoL as well as treatment efficacy of palbociclib-based therapy in the approved indications.
Eligible patients had proven diagnosis of HR+/HER2- locally advanced or MBC and were either candidates to receive palbociclib in combination with aromatase inhibitor (first-line) or candidates to receive palbociclib in combination with fulvestrant (later-lines) for their locally advanced or MBC.[vi]
Patients were randomly assigned (2:1) to CANKADO-active arm or CANKADO-inform arm. In the CANKADO-active arm patients used fully functional CANKADO-based eHealth treatment support service, including documentation of daily drug intake, daily general health, symptoms, feedback functions (PRO-React) and on-site FACT-B (Functional Assessment of Cancer Therapy-Breast) surveys. Patients randomized to CANKADO-inform arm used an eHealth service comprising only personal login and documentation of daily drug intake, on-site FACT-B surveys, but no symptom documentation and no feedback functions.
In the PreCycle trial, researchers wanted to investigate whether therapy support by the CANKADO PRO-React application can improve QoL in patients with HR+/HER2+ MBC treated with endocrine therapy + palbociclib.
The study was prematurely terminated due to COVID-19 pandemic in December 2021.[vii]
The first author, Prof. Dr. Nadia Harbeck (on behalf of all co-authors) and the legal trial sponsor, palleos healthcare, and, would like to thank to all patients who participated in PreCycle, all PreCycle investigators and PreCycle site teams, ECCO-AACR-EORTC-ESMO Workshop on Methods in Clinical Cancer Research (MCCR 2016) for support in protocol development, iOMEDICO for participation in trial conduct, CANKADO for eHealth support, and Pfizer for financial trial support.
[i]Cardoso F, Paluch-Shimon S, Senkus E, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol 2020; 31:1623–1649.
[ii] Lüftner D, Fasching PA, Haidinger R, et al. ABC6 Consensus: Assessment by a Group of German Experts. Breast Care (Basel). 2022 Feb;17(1):90-100.
[iii] 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; 318:197–198.
[iv] Denis F, Lethrosne C, Pourel N, et al. Randomized trial comparing a web-mediated follow-up with routine surveillance in lung cancer patients. J Natl Cancer Inst 2017;109(9).
[v] Whynes DK; TOMBOLA Group. Correspondence between EQ-5D health state classifications and EQ VAS scores. Health Qual Life Outcomes 2008; Nov 7; 6:94.
[vi] Degenhardt T, Fasching PA, Lüftner D, et al. PRECYCLE: multicenter, randomized phase IV intergroup trial to evaluate the impact of eHealth-based patient-reported outcome (PRO) assessment on quality of life in patients with hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer treated with palbociclib and an aromatase inhibitor or palbociclib and fulvestrant. Trials. 2023 May 17;24(1):338.
[vii] Harbeck N, Fasching PA, Wuerstlein R, et al. Significantly longer time to deterioration of quality of life due to CANKADO PRO-React eHealth support in HR+ HER2- metastatic breast cancer patients receiving palbociclib and endocrine therapy: Primary outcome analysis of the multicenter randomized AGO-B WSG PreCycle trial. Ann Oncol. 2023 May 16:S0923-7534(23)00684-1.