OBJECTIVES: To assess the validity of patient-reported outcomes (PRO) from the open label COLUMBUS trial, patients’ answers were checked against objective safety measures, as recommended by health authorities when blinding is not feasible. METHODS: In COLUMBUS, a phase III, randomized, open label, multicenter trial, the combination encorafenib 450mg once daily plus binimetinib 45mg twice daily (N=192) demonstrated significantly longer progression-free survival versus vemurafenib 960mg twice daily (N=191) in unresectable/metastatic BRAF-mutant melanoma patients. Post-hoc analyses were performed on the validated PROs ‘Functional Assessment of Cancer Therapy–Melanoma’ (FACT-M) and ‘European Organization for Research and Treatment of Cancer’s Quality of Life Questionnaire–Core 30’ (EORTC QLQ-C30). Symptom items directly related to adverse events (AE) were identified among 43 FACT-M and 30 QLQ-C30 items. Patient-level answers to these items (e.g. FACT-M ‘had nausea’) were summarized by presence/absence of the related AE (e.g. ‘nausea’) the week before questionnaire completion, corresponding to the PROs recall period. All patient-visits were pooled and analyzed independently. Item score ranges are 0-4 (FACT-M) and 1-4 (QLQ-C30); higher scores indicate more symptoms. RESULTS: About 6,500 patient-visits were analyzed. For FACT-M ‘nausea’ item and QLQ-C30 ‘nausea’, ‘diarrhea’, ‘vomiting’, ‘insomnia’ and ‘constipation’ items, patients experiencing the related AE the week before PRO completion scored on average 0.58-0.94 points higher than those without the specific AE reported. For these items, median scores were 1-point higher in patients with vs. without the AE. Smaller score differences were observed with control items indirectly related to the AE (0.12-0.57). These results were observed independently of the treatment arm. CONCLUSIONS: The association of PROs with safety results across a range of symptoms supports the validity of PROs collected in COLUMBUS. Given the importance of the patient’s perspective in the overall therapy assessment, the COLUMBUS quality of life data provides relevant information in complement to the clinical outcomes.