Treatment-Related Adverse Events

In the prior MAPLE trial, grade ≥3 adverse events at 3 months occurred in 50.9% of the intervention arm compared with 66.4% of the usual care arm. Patient-reported adverse events are measured using the 12 core symptom items from the NCI PRO-CTCAE, with the Japanese version linguistically and psychometrically validated. Treatment modifications within 3 months — including dose reductions, switching from combination to monotherapy, or discontinuation — are tracked as a secondary health outcome. In MAPLE2, grade ≥3 adverse events within 3 months are evaluated by oncologists and nurses using NCI CTCAE V.5.0. Grade ≥3 adverse events within 3 months is planned as the primary endpoint for the future definitive multicentre hybrid effectiveness-implementation RCT.