Multicentre trial of telemonitored circadian rhythms and electronic patient-reported outcomes (ePROs) for improving tolerability of initial mFOLFIRINOX cycles in patients (pts) with advanced pancreatic ductal adenocarcinoma (PDAC): MultiDom (NCT04263948).

Abstract

4204 Background: Severe Adverse Events (SAEs) requiring emergency admissions (EAs) alter quality of life and treatment efficacy, and increase health costs. Toxicities, EAs, and reduced survival have been linked to the disruption of circadian rhythms, whose relevance is tested here in a multicentre, prospective, longitudinal, single-arm interventional trial. Methods: Continuous telemonitoring and automatic analyses of circadian rhythms and daily body weight and ePROs over 50 days (d) aim to reduce EAs in PDAC pts receiving the first 3 cycles of mFOLFIRINOX. The hypothesis (H 0 ) is that EAs involve <15% of the pts, rather than a historical rate of 15-30%. Pts data were collected through telecommunicating chest sensor, balance and tablet connected to a multidimensional digital platform. The main circadian parameter was (I<O), the % of accelerations per min In-Bed that are below the median accelerations per min Out-of-Bed. Control(I<O) is 97-100%. An (I<O) ≤96% defined circadian disruption. Electronic alerts were sent out if (I<O) ≤96%, body weight loss ≥5%, or self-rated symptoms ≥7 using the MD Anderson Symptoms Inventory (MDASI). Results: 28 males and 24 females had a median age of 65 years (33-82), and WHO performance status of 0-1 in 92% of them. PDAC was metastatic in 69% of cases, including liver in 50%. An EA occurred in 2 pts (3.8% [95% CL, 1.1-13%]), thus validating H 0 . SAEs in both EA pts were grade (Gr) 3 febrile neutropenia and diarrhea; and Gr 3 leuco-neutropenia and hypokaliemia respectively. Symptom-free circadian disruption preceded EA by 8 d in both pts. Circadian disruption occurred at least once in 65-75% of the pts on treatment, and lasted > 20 d in 27 pts (52%). Severe fatigue and anorexia were self-reported by 62% and 58% of the treated pts respectively. Main Grade 3-4 toxicity was neutropenia in 17% of the pts [95% CL, 9-30]. Disease control rate at 2 months was 75% [53-100]. Multidom revealed (i) a high level of pt engagement supported both by data compliance rates of 84-92% for circadian rhythms, 93-100% for body weight, and 86-100% for ePROs; and by median duration of platform use of 46 d (IQR, 38-50]; (ii) 1881 medical type e-alerts for circadian disruption (43%), MDASI symptoms (25%), and body weight loss (12%); (iii) 883 categorized responses to medical e-alerts, and (iv) highest global score of self-rated pt experience of participation (median, 5/5 (4 to 5). Conclusions: Combining telemonitoring of circadian rhythms, body weight and symptoms in remote PDAC pts on mFOLFIRINOX revealed potential benefit on pts real life through informed proactive telecare, and likely improved treatment safety. Actual benefits from such telemonitoring-telecare platform with circadian metrics need further confirmation in trials involving pts at risk of SAEs. Clinical trial information: NCT04263948 .