Evaluating clinically meaningful change of the EORTC QLQ-C30 in patients with NSCLC

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.