Presentation (CTI)

OBJECTIVES: A summary measure assessing patient-reported overall side-effect (SE) bother to inform the tolerability of a treatment in cancer clinical trials is recommended by the US FDA. The objective is to confirm the FACT-GP5 score 3-4 as the optimal categorization of high SE bother among patients with mantle cell lymphoma (MCL).
METHODS: BRUIN MCL-321 is a phase 3, global, randomized, open-label trial comparing pirtobrutinib to investigator’s choice of covalent BTK inhibitor in previously treated MCL. Blinded, pooled data were used. Three categorizations of high versus no/low SE bother (GP5 scores: 3-4 versus 0-2; 4 versus 0-3; 2-4 versus 0-1) were used to evaluate the ability of the GP5 to discriminate functioning and global health status/quality of life (GHS/QoL) as measured by the EORTC QLQ-C30. The distributions of QLQ-C30 scores (higher scores represent better outcomes) were classified by high and no/low SE bother categories, supplemented by t-test and boxplot visualization.
RESULTS: Data from 523 participants were included in this FACT-GP5 analysis. High SE bother defined as a rating of 3-4 (n=40 assessments) showed best separation from no/low bother (n=1723 assessments) for the QLQ-C30 Physical Functioning scale, with non-overlapping interquartile ranges (IQR) of 36.7-66.7 for high (mean±standard deviation: 51.0±23.1) and 80.0-100.0 for no/low SE bother (86.9±16.0), p<.0001. Other categorizations had overlapping IQRs and mean values that were closer to each other. QLQ-C30 Role, Social, Emotional, Cognitive and GHS/QoL scores each had overlapping IQRs with all categorizations; group means for the 3-4 versus 0-2 categorization were further apart than the others. Few participants rated SE bother with a score of 4 (n≤7 assessments), limiting interpretation for corresponding categorization.
CONCLUSIONS: The definition of high SE bother based on FACT‑GP5 rating of 3-4 was confirmed as the most appropriate for defining the tolerability endpoint in BRUIN-MCL-321.