Based on European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) outputs from the LUME-Colon 1 study, we compared and discussed different statistical methods for evaluating health-related quality of life data in oncology clinical trials. The different analyses consistently showed that patients' overall global health status/quality of life status was not impaired by active treatment with nintedanib versus placebo, and that patients perceived some benefits with nintedanib compared with placebo. Introduction: We used European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) data from the LUME-Colon 1 study to illustrate different methods of statistical analysis for healthrelated quality of life (HRQoL), and compared the results. Patients and Methods: Patients were randomized 1:1 to receive nintedanib 200 mg twice daily plus best supportive care (n ¼ 386) or matched placebo plus best supportive care (n ¼ 382). Five methods (mean treatment difference averaged over time, using a mixed-effects growth curve model; mixed-effects models for repeated measurements (MMRM); time-to-deterioration (TTD); status change; and responder analysis) were used to analyze EORTC QLQ-C30 global health status (GHS)/QoL and scores from functional scales. Results: Overall, GHS/QoL and physical functioning deteriorated over time. Mean treatment difference slightly favored nintedanib over placebo for physical functioning (adjusted mean, 2.66; 95% confidence interval [CI], 0.97-4.34) and social functioning (adjusted mean, 2.62; 95% CI, 0.66-4.47). GHS/QoL was numerically better with nintedanib versus placebo (adjusted mean, 1.61; 95% CI, À0.004 to 3.27). MMRM analysis had similar results, with better physical functioning in the nintedanib group at all timepoints. There was no significant delay in GHS/QoL deterioration (10%) and physical functioning (16%) with nintedanib versus placebo (TTD analysis). Status change analysis showed a higher proportion of patients with markedly improved GHS/QoL and physical functioning in the nintedanib versus placebo groups. Responder analysis showed a similar, less pronounced pattern. Conclusion: Analyses of EORTC QLQ-C30 data showed that HRQoL was not impaired by treatment with nintedanib versus placebo. Analysis and interpretation of HRQoL endpoints should consider symptom type and severity and course of disease.