Quality of life (QoL)-based end-points for patients with advanced pancreatic ductal adenocarcinoma (aPDAC): Results from the PanDA prospective observational study

Abstract

Background: Adequate design of clinical trials using QoL-based primary-end points to assess benefit derived from supportive interventions such as exercise, nutrition or complementary therapies is challenging in PDAC due to a lack of available data describing baseline QoL and changes over time for this patient population. Methods: PanDA was a prospective observational study of prevalence, assessment and treatment of pancreatic exocrine insufficiency in patients with aPDAC (NCT03616431). QoL data using the EORTC QlQ-C30 and QLQ-PAN26 questionnaires were collected for the follow-up cohort at baseline (BSL), week6 (W6) and month3 (M3). This post-hoc analysis included patients with aPDAC and explored the mean and standard deviation (SD) of the Physical Functioning Scale (PhFS) at BSL, W6, M3) and mean (SD) intra-patient changes over time (W6-BSL and M3-BSL). Subgroup analysis by stage (locally-advanced vs metastatic) was also performed. Percentage of patients evaluable at each time point was reported. Descriptive statistical analysis was per- formed (Stata v.17). Results: Of 37 patients recruited into the follow-up cohort, 32 met eligibility criteria for this post hoc analysis. Thirty (93.8%), 17 (53.1%; all had paired BSL data) and 13 (40.6%; all had paired BSL data) patients were evaluable with PhFS data available at BSL, W6 and M3, respectively. PhFS (mean (SD); number of observations) did not vary over time when all patients were analysed together (BSL: 76.17(26.46);30) (W6: 79.18(12.74);17) (M3: 74.46(16.76);13). Intra-patient mean changes at W6 (-6.59(15.13);17) or M3 (-5.46(24.82);13). Subgroup analysis identified that changes in W6 were more marked in patients with metastatic disease (-12.14(15.54);7) compared to locally advanced (-2.70(14.32);10). Conclusions: Changes on PhFS over time were likely impacted by selection bias. Intra- patient mean changes at W6 or M3 seemed more reliable to be utilised as primary- end point and sample size calculation in future clinical trials. Subgroup analysis identified that changes in W6 were more marked in patients with metastatic Intra- patient changes rather than pooled results may be more reliable when designing clinical trials with QoL-based primary end-points in aPDAC. W6 assessment may be most informative, as waiting until M3 may compromise the power of the study due to significant drop out.