Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC)

We investigated the impact of durvalumab f tremelimumab versus chemotherapy on patient-reported symptoms, functioning, and global health status/quality of life in the phase 3 MYSTIC trial of metastatic non- small-cell lung cancer in patients with tumor cell programmed cell death ligand 1 expression > 25%. Durvalumab f tremelimumab reduced symptom burden and improved times to deterioration, suggesting there were no detrimental effects with treatment. Background: The phase 3 MYSTIC study of durvalumab f 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 naive patients were randomized (1:1:1) to dur valumab, dur valumab + 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 ( N = 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), durvalumab + 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] = 0.7; 95% CI, 0.5-1.0), durvalumab +tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab +tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab +tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab +tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 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.