Relationships Between Clinician-Confirmed Symptomatic Progression and Change in Patient-Reported Outcomes in...

Time to symptomatic progression is a novel endpoint used in cancer clinical trials. It is of scientific interest to understand the relationship between clinician-confirmed symptomatic progression and patient-reported experiences. The current work evaluates whether and how changes in patient-reported outcome (PRO) measures relate to the timing of first documentation of a symptomatic progression event.

Data were utilized from the phase 3 MARIPOSA study of patients with previously untreated epidermal-growth-factor-receptor-mutated locally advanced or metastatic non-small-cell lung cancer (NSCLC). Relationships between symptomatic progression events and 4 PROs (EORTC-QLQ-C30 global health status, physical and role functioning, and the NSCLC-SAQ total score) were examined. Longitudinal changes in the PRO measures pre- and post-symptomatic progression were modeled using piecewise mixed effect models with a subgroup of patients that experienced a symptomatic progression event.

Of the N = 1074 patients in MARIPOSA, 362 patients met criteria for symptomatic progression. This patient group's median age was 64 years old, and just over half were Asian (n = 203, 56.1%) and female (n = 198, 54.7%). Across all PROs, scores began to significantly worsen by 9 months before progression (P < .01) and continued to worsen more rapidly as the date of progression approached (eg, in the final 2 months leading up to progression, rates of worsening were largest in magnitude [P < .0001]). Scores also continued worsening from progression forward (P < .05).

Consistent associations between symptomatic progression and worsening in patient-reported symptoms and health-related quality of life over time support the patient relevance of time to symptomatic progression as an endpoint in NSCLC.