OBJECTIVES:  The EORTC QLQ-C30 has been extensively validated in cancer patients, but its responsiveness to individual changes in clinical outcomes in anaplastic lymphoma kinase (ALK+) non-small cell lung cancer (NSCLC) was not previously evaluated. The ALK in Lung Cancer Trial of brigatinib (ALTA trial; NCT02094573), an open-label, Phase 2, randomized, multicenter, international study, evaluated the efficacy and safety of brigatinib (Arm A: 90 mg qd and Arm B: 180 mg qd with a 7-day lead-in at 90 mg) in patients (pts) with locally advanced or metastatic ALK+ NSCLC whose disease had progressed on prior therapy with crizotinib. To interpret meaningful change in patient-reported outcomes (PROs), the responder definition (RD) threshold for the minimum individual pt change representing treatment benefit was established. METHODS:  PRO data collection included the EORTC QLQ-C30 at baseline and first day of each cycle. The RD of the Global Health Status (GHS)/QOL scale of the QLQ-C30 was examined with anchor and distribution-based methods. Anchors included time point response per RECIST v.1.1 criteria and ECOG performance status. RESULTS:  Of 222 randomized pts, 208 (94%) completed PRO data at baseline and at least one subsequent on treatment visit. The ANCOVA adjusted (sex and age) mean group difference between pts with stable disease (n=76) vs. complete or partial response (n=99) in change from baseline to cycle 3 in GHS/QOL was 9.8. Distribution-based estimates of the RD were 5.04, 12.6 and 17.6 (0.2 SD, 0.5, SD, and 1.0 SEM). A change of 8.33 (1 point on the raw scale, the minimum change possible) was selected as the RD threshold for GHS/QOL based on corresponding changes in response at cycle 3. CONCLUSIONS:  A change of 8.33 points from baseline to cycle 3 can be interpreted as a meaningful score change in GHS/QOL indicative of treatment benefit for an individual patient with ALK+ NSCLC.