RESUMEN
BACKGROUND: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs). PATIENTS AND METHODS: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumabâ¯+â¯tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests. RESULTS: There were no between-arm differences in baseline PROs (Nâ¯=â¯488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (-9.5; 99% confidence interval [CI], -17.0 to -2.0), durvalumabâ¯+â¯tremelimumab (-11.7; 99% CI, -19.4 to -4.1); and for C30 appetite loss: durvalumab (-11.9; 99% CI, -21.1 to -2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR]â¯=â¯0.7; 95% CI, 0.5-1.0), durvalumabâ¯+â¯tremelimumab (HRâ¯=â¯0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HRâ¯=â¯0.6; 95% CI, 0.4-0.8), durvalumabâ¯+â¯tremelimumab (HRâ¯=â¯0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HRâ¯=â¯0.6; 95% CI, 0.5-0.9), durvalumabâ¯+â¯tremelimumab (HRâ¯=â¯0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumabâ¯+â¯tremelimumab (HRâ¯=â¯0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HRâ¯=â¯0.5; 95% CI, 0.4-0.7), durvalumabâ¯+â¯tremelimumab (HRâ¯=â¯0.7; 95% CI, 0.5-0.9) (both C30). CONCLUSION: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.