BackgroundAdjuvant treatment decision-making based on conventional clinical/pathological and prognostic single molecular markers or genomic signatures is a therapeutic area in which over-/under-treatment are still key clinical problems even though substantial and continuous improvement of outcome has been achieved over the past decades. Response to therapy is currently not considered in the decision-making procedure.ADAPT is one of the first new generation (neo)adjuvant trials dealing with individualization of (neo)adjuvant decision-making in early breast cancer and aims to establish early predictive surrogate markers, e.g., Ki-67, for therapy response under a short induction treatment in order to maximally individualize therapy and avoid unnecessary toxicity by ineffective treatment.Methods/designThe prospective, multi-center, controlled, non-blinded, randomized, investigator initiated phase II/III ADAPT trial has an innovative “umbrella” protocol design. The “umbrella” is common for all patients, consisting of dynamic testing of early therapy response. ADAPT will recruit 4,936 patients according to their respective breast cancer subtype in four distinct sub-trials at 80 trial sites in Germany; 4,000 patients with hormone receptor positive (HR+) and HER2 negative disease will be included in the ADAPT HR+/HER2- sub-trial, where treatment decision is based on risk assessment and therapy response to induction therapy, and 380 patients will be included in ADAPT HER2+/HR+. A further 220 patients will be included in ADAPT HER2+/HR- and 336 patients will be recruited for ADAPT Triple Negative. These three sub-trials focus on identification of early surrogate markers for therapy success in the neoadjuvant setting. Patients will be allocated to the respective sub-trial according to the result of their diagnostic core biopsy, as reported by local/central pathology for HR and HER2 status.DiscussionRecent trials, such as the GeparTrio, have shown that response-guided therapy using clinical response may improve outcome. For chemotherapy or HER2-targeted treatment, pathologic complete response in a neoadjuvant setting is an excellent predictor of outcome. For endocrine therapy, response to short induction treatment – as defined by decrease in tumor cell proliferation – strongly correlates with outcome. ADAPT now aims to combine static prognostic and dynamic predictive markers, focusing not just on single therapeutic targets, but also on general markers of proliferation and cell death. Biomarker analysis will help to optimize selection of subtype-specific treatment.Trial registrationClinicalTrials.gov: ADAPT Umbrella: NCT01781338; ADAPT HR+/HER2-: NCT01779206; ADAPT HER2+/HR+: NCT01745965; ADAPT HER2+/HR-: NCT01817452; ADAPT TN:NCT01815242.

BackgroundElectronic health (eHealth) and mobile communication-based health care (mHealth) applications have been increasingly utilized in medicine over the last decade, and have facilitated improved adherence to therapy regimens in patients with chronic conditions. Due to the long duration of breast cancer therapy, and the long course of disease in metastatic breast cancer, a need for more intensified physician-patient communication has emerged. Various support mechanisms, including new media such as mHealth and eHealth, have been proposed for this purpose.ObjectiveThe aim of this study was to analyze the correlation between sociodemographic factors, as well as health status of breast cancer patients, and their current utilization of new media, or their willingness to use Internet and mobile phone apps for improvement of therapy management.MethodsThe survey for this study was conducted anonymously during the 2012 Mamazone Projekt Diplompatient meeting (Augsburg, Germany), which hosted approximately 375 participants per day. A total of 168 questionnaires were completed. The questionnaire aimed to assess sociodemographic status, disease patterns, and current use of new media (ie, Internet, mobile phone, and mobile phone apps) in breast cancer patients. Habits and frequency of use for these new technologies, as well as patients’ affinity towards eHealth and mHealth tools for therapy management improvement, were investigated.ResultsAlmost all participants used the Internet (95.8%, 161/168), with 91.5% (151/165) also utilizing this technology for health-related issues. Approximately 23% (38/168) of respondents owned a mobile phone. When asked about their preferences for therapy assistance, 67.3% (113/168) of respondents were interested in assistance via the Internet, 25.0% (42/168) via mobile phone, and 73.2% (123/168) via call center. Patients diagnosed with breast cancer <5 years before the survey were significantly more interested in a call center than patients diagnosed >5 years before survey participation.ConclusionsThe vast majority of breast cancer patients accept the Internet for therapy assistance, which indicates that eHealth is a promising medium to improve patient-physician communication. Such technologies may improve individual disease management and ultimately lead to an enhanced adherence to therapy regimens.

The introduction of new therapeutic agents, such as fludarabine phosphate (Fludara) and alemtuzumab (MabCampath, Campath), has made it possible to treat B-cell chronic lymphocytic leukemia (B-CLL) more effectively, compared with alkylating agents. However, although an increasing number of patients are able to achieve complete remission (CR), relapse is almost inevitable, because of the re-emergence of the malignant clone from small numbers of residual malignant cells. This phenomenon has introduced a need for a more sensitive assessment of low-level disease which, in turn, has encouraged the development of therapies aimed at the eradication of all residual disease in CR patients. The eradication of residual disease is associated with improved remission durability and has great potential in offering the possibility of cure. Alemtuzumab is the foundation of many eradication-based treatment approaches because of its ability to achieve clinical remissions and to successfully purge minimal residual disease (MRD) from both blood and bone marrow in B-CLL patients. This article describes and compares polymerase chain reaction (PCR) and flow cytometric methodologies for the assessment of MRD, and presents data demonstrating that alemtuzumab can eliminate residual malignant cells from blood and bone marrow (whether assessed by PCR or flow cytometry) at the highest levels of sensitivity currently available. The ability to clear MRD from bone marrow in patients achieving clinical CR using alemtuzumab is a significant step forward in the treatment of B-CLL, and supports treatment strategies in which alemtuzumab is used in combination with other agents. Purging of MRD from both blood and bone marrow also enables patients to proceed to autologous hematopoietic stem cell transplantation, a strategy that is able to achieve long-term remission.

TPS601 Background: The WSG ADAPT trial program represents the concept of individualization of (neo)-adjuvant decision-making in EBC in a subtype-specific manner. The first WSG ADAPT umbrella trial aimed to establish early predictive molecular surrogate markers for response after a short 3-week induction treatment. The goals of the WSG ADAPT trial program are early response assessment and subtype-specific therapy tailoring to those patients who are most likely to benefit. Methods: WSG-ADAPTcycle is a prospective, multi-center, interventional, two-arm, open-label, (neo)adjuvant, non-blinded, randomized, controlled phase III trial (NCT04055493). It investigates whether patients (pts.) with HR+/HER2- EBC identified during screening as intermediate risk (based on Oncotype DX and response to 3 weeks of preoperative endocrine therapy [ET]) derive additional benefit from 2 years of the CDK4/6 inhibitor ribociclib combined with ET compared to chemotherapy (CT) (followed by standard ET). Co-primary endpoints are disease-free survival (DFS) and distant DFS. It is planned to screen 5600 pts and to randomize 1670 pts in a 3:2 ratio (ribociclib + ET/CT). Study start was in July 2019 (80 sites, enrollment period 36 months) and until date of submission, 180 pts. have been screened and 40 randomized. Pts with HR+/HER2- EBC with clinically enhanced risk (cT2-4 or Ki67 20% or G3 or cN+) are eligible if they fulfill the ADAPT intermediate-risk group criteria: either Recurrence Score (RS) ≤25 and Ki67postendocrine>10%, RS >25 and Ki67postendocrine<10% in p/cN0-1 pts, or RS ≤25 and Ki67postendocrine<10% in c/pN2-3 pts. Treatment duration is 2 years for the ribociclib + ET (premenopausal: AI + GnRH) arm and 16-24 weeks for the CT arm; treatment is possible either in the neoadjuvant (ET + ribociclib duration 16 – 32 weeks) or adjuvant setting. ePROs are collected using CANKADO; ECG monitoring is performed using a novel cardiology-supported CANKADO-based eHealth method. Translational analyses: Exploratory tissue biomarker research will be conducted to assess alterations in molecular markers. In addition, ctDNA/ctRNA from optional blood samples will be assessed for mutations and gene expression. Conclusions: ADAPTcycle seeks to evaluate whether endocrine-based therapy with ET and a CDK 4/6 inhibitor is superior to CT followed by ET in patients with luminal EBC who may be undertreated with ET alone (based on either lack of endocrine responsiveness or high tumor burden). Clinical trial information: 2018-003749-40 .

In an outpatient setting, some challenges of cancer treatment include continuous patient–physician communication, lack of adherence, potential side effects and their impact on quality of life and other patient-reported outcomes. These challenges in the support of disease management can be overcome by the introduction of eHealth applications. Though the market of eHealth applications is fast growing, many applications lack evidence regarding their effectiveness, safety and utility. Only few prospective randomized trials have been conducted, so far. Results of these studies univocally show a gain in health-related quality of life, in the examined eHealth applications. It remains unclear if procedural and cost efficacy are affected by eHealth applications. The upcoming PreCycle study will be the largest randomized eHealth study in oncology.

Patient-reported outcome measures obtained via E-Health tools ease the assessment burden and encourage patient participation in cancer care (PaCC Study) Background E-health based patient-reported outcome measures (PROMs) have the potential to automate early identification of both nutrition status and distress status in cancer patients while facilitating treatment and encouraging patient participation. This cross-sectional study assessed the acceptability, accuracy, and clinical utility of PROMs collected via E-Health tools among patients undergoing treatment for stomach, colorectal, and pancreatic tumors. Results Eight-nine percent mostly, or completely, agreed that PROMs via tablets should be integrated in routine clinical care. Men were significantly more likely to require help completing the questionnaires than women (inv.OR= 0.51, 95% CI=(0.27, 0.95), p = 0.035). The level of help needed increased by 3% with each 1-year increase in age (inv. OR=1.03, 95% CI=(1.01, 1.06), p = 0.013). On average, a patient tended to declare weight which was 0.84 kg inferior to their true weight (Bland and Altman 95 % CI=(-3.9, 5.6); SD: 2.41) and a height which was 0.95 cm superior to their true height (Bland and Altman 95 % CI=(−5, 3.1); SD 2.08). Patient-reported nutrition status was significantly associated with the professionally generated assessment (95% CI=(2.27, 4.15), p < 0.001). As nutrition status declined, the distress score increased (95%CI=(0.88, 1.68), p < 0.001). Of the patients, 48.8% who were both distressed and malnourished requested supportive care to address their problems. Conclusion Patient-reported assessments utilizing E-health tools are an accurate and efficient method to encourage patient participation in cancer care while simultaneously ensuring that regular assessment of psycho-social and nutritional aspects of care are efficiently integrated in the daily clinical routine.

BackgroundLack of adherence and compliance with drug regimens among breast cancer patients represent substantial problems in oral therapies, leading to significant impacts on mortality. Where other systems have failed, electronic health (eHealth) could be a possible solution to improve medication intake, along with the doctor-patient relationship. Initial results from studies concerning new interventions for therapy support are promising, but reports suggest that general acceptance of new treatment support tools is needed among patients and physicians alike.ObjectiveThe aim of this study was to investigate the actual use of the Internet and other modern media among physicians involved in breast cancer treatment.MethodsUsing a standardized questionnaire, actual utilization of new media among physicians was analyzed. Internet-related behaviors in private, as well as in business life, were investigated. Attention was focused on physicians’ opinions regarding modern eHealth tools and how patients could be best supported to enhance adherence.ResultsA total of 120 physicians, all participating in breast cancer care, completed the questionnaire (median age 41 years). Almost all participants (99.2%, 119/120) used the Internet for general purposes and 98.3% (118/120) used it for medical issues as well. Virtually all medical professionals (99.2%, 119/120) reported that they owned a computer, while more recently invented technologies such as tablets and smartphones were owned by 31.9% (38/119) and 73.1% (87/119), respectively. The Internet was favored by 66.4% (79/119) of the physicians in our survey as a source for patient support; 71.2% (84/118) would also favor modern media for side effect registration. Based on our analysis, the most frequent Internet-utilizing physicians were characterized by age <60, worked in a hospital, and were employed as a junior physician.ConclusionsThis study demonstrated a high usage of Internet-related technologies among physicians, indicating that the use of eHealth for advanced and individualized support in breast cancer care is a promising addition to treatment management. Such technologies have the potential to enhance adherence and compliance in therapy among cancer patients.

2083 Background: PreCycle (NCT03220178), a multicenter, randomized phase IV Intergroup trial evaluates the impact of ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer patients (pts) treated by palbociclib (P) and an aromatase inhibitor or P+fulvestrant. Pts willing to use the web/APP-eHealth solution CANKADO are eligible. Patients are randomized (2:1, stratified by therapy line) to the active (CANKADO PRO-React) or inactive inform arm. Primary endpoint is time to deterioration (TTD) of QoL. Methods: The trial started in 2017 and is ongoing (81 centers); regular safety reports are routinely provided to the study sponsor. Analysis of distribution of serious adverse events (SAE) was initiated by the trial leadership and performed using the Oct 15, 2019 safety report. Data that could bias primary or secondary endpoints were not analyzed. Bayesian inference (non-informative prior) was used to estimate probabilities; no corrections for potential multiplicities were made. Results: At data cut-off, 261/281 randomized patients had received study medication and provided CANKADO documentation. At time of evaluation, a total of 40298 days were documented. CANKADO was used on 59% (+/-10%) of all days over a 2-year period. SAEs were observed in 26/175 (14.9%) of all active-arm patients vs. 18/86 (20.9%) of inform-arm patients (90% probability of reduction in inform patients). Total SAEs were 36 (active) vs. 27 (inform); corresponding SAE incidence per hundred patients was 20.6 vs. 31.4, a relative reduction of about one-third. Conclusions: CANKADO is well accepted and used regularly by pts in PreCycle, so far over a 2-year period. The present (unplanned) analysis suggests a potentially substantial, clinically relevant reduction in relative SAE incidence among 1stL pts using PRO-React, with a more modest decrease overall. This analysis is preliminary, representing a snapshot, and cannot provide a definitive explanation for the observed SAE reduction. PreCycle will continue to enroll patients in order to further evaluate the potential benefits of interactive eHealth support. Collaborators: WSG WOMEN´S HEALTHCARE STUDY GROUP, CANKADO, Pfizer, AGO-TraFo, AGO-B, Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie e.V. Sponsor: Palleos Healthcare GmbH Keywords: eHealth, Adverse Events, Palbociclib Clinical trial information: NCT03220178.