OBJECTIVES: Health status, burden of illness and quality of life are considered crucial for clinical decision making in lung cancer.  The purpose of this study was to provide the statistical results associated with the patient-reported outcome endpoints at the conclusion of this Phase 3, randomized, open-label, multinational study of Amrubicin compared with Topotecan. METHODS: Change in quality of life from Cycle 1 to end-of-study focused on change in lung cancer symptom and domain scores as well as minimally clinical important difference (MCID) as measured by the 9-item Lung Cancer Symptom Scale.  Longitudinal Mixed Models were conducted adjusting for Treatment, Disease Stage, Previous Treatment Response, and Time to Drop Out.  MCID was calculated as 1 standard error of measurement from baseline to end of study.  Additionally, change in individual symptom scores on the LCSS for appetite, cough, dyspnea, fatigue, heomptysis, and pain were evaluated descriptively. RESULTS: A total of 607 patients were included in the study at baseline.  Follow-up LCSS data was available on 51.7% of Amrubicin and 46.2% of Topotecan patients.  Amrubicin showed greater clinical improvements on LCSS total score and symptom burden as measured by the MCID analysis as well as the longitudinal analysis.  Specifically, 65% of patients on Amrubicin improved or demonstrated no change on the LCSS Symptom Burden Score compared to 52% of Topotecan patients.  On the same scale, 30.25% of Topotecan patients worsened compared to 20.24% of Amrubicin patients (MCID=8.17; Chi-Square = 6.70, p = 0.0822). CONCLUSIONS: Amrubicin has better symptom control (and QOL vs. Topotecan) on all symptoms (equivalence on hemoptysis).  Subgroup analyses are consistent and are all in favor of Amrubicin (survival, previous response, disease stage, and study response).  Refractory patients later treated with Amrubicin have greater symptom control and QoL vs. Topotecan.