Background: The PANAMA study demonstrated superior progression-free survival (PFS) with the addition of panitumumab (Pmab) to fluorouracil and folinic acid (FU/FA) as maintenance therapy following first-line induction therapy with FOLFOX/Pmab in patients with RAS wild-type metastatic colorectal cancer. We report health-related quality of life (HRQOL) analyses of the PANAMA study. Methods: HRQOL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at every cycle of therapy until disease progression. All patients who received at least one dose of induction therapy and completed at least one HRQOL assessment were included into the analysis. HRQOL outcomes were mean changes in EORTC QLQ-C30 from baseline (prior to cycle 1 of induction therapy) to each cycle of treatment (both induction and maintenance therapy). The trial is registered with ClinicalTrials.gov (NCT01991873). Results: In total, 349/377 (93%) of the induction and 237/248 pts (96%) of the maintenance group completed at least one HRQOL assessment and were included in the HRQOL analysis population. There were no significant differences in any of the EORTC QLQ-C30 items between both treatment arms before induction therapy and at randomization. From baseline to cycle 6 of induction therapy there was significant improvement in mean EORTC QLQ-C30 global health status (GHS)/QOL, functioning (except for cognitive functioning) and symptom (except for nausea and vomiting, dyspnea, appetite loss, constipation, and financial difficulties) scores in the randomized population. During maintenance therapy, no significant differences between FU/FA plus Pmab and FU/FA alone were observed. In both arms of the trial, GHS/QOL scores were maintained or trended to improve from baseline (start of induction therapy) to cycle 10 of maintenance therapy (FU/FA plus Pmab: mean difference 9.48 [95% CI 1.96-17.00]; p=0.014); FU/FA arm (mean difference 6.52 [95% CI –1.9-14.95]; p=0.128). Conclusions: Using the established EORTC QLQ-C30 assessment, the addition of Pmab to FU/FA as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer did not impair the HRQOL endpoints analyzed compared to FU/FA alone. These results, along with previously reported improvement in PFS, may support clinical decision-making concerning maintenance treatments. Clinical trial information: NCT01991873.