Association Between Patient-Reported Outcomes and Overall Survival in Patients with Advanced NSCLC Treated with First-Line Cemiplimab-Based Therapy

<b>Background/Objectives</b>: Research on the association between change from baseline in patient-reported outcomes (PROs) and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) exists. This study evaluated the association between post-baseline PROs and OS in patients with advanced NSCLC who received first-line cemiplimab-based therapy. <b>Methods</b>: We evaluated PRO data from two phase III studies (EMPOWER-Lung 1 [NCT03088540] and EMPOWER-Lung 3 [NCT03409614]) using a Cox proportional hazards model. Twelve pre-specified PRO scales from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Lung Cancer 13 module were evaluated. Landmark analyses were conducted at 3, 6, 9, and 12 months. Time-dependent analyses using change from baseline PROs as a time-dependent covariate were conducted to evaluate the association of post-baseline PRO improvement with OS. <b>Results</b>: At the 3-month landmark, we observed a 56% reduction in the risk of death (HR = 0.44; 95% CI: 0.32-0.62; nominal <i>p</i> < 0.0001) among stable/improved vs. worsened/unobserved PROs for global health status (GHS)/quality of life (QoL). Results at the 6-, 9-, and 12-month landmarks of GHS/QoL were consistent with those at the 3-month landmark. Time-dependent analyses showed that every 10-point improvement in GHS/QoL was associated with a 31% reduction in the risk of death (HR = 0.69; 95% CI: 0.64-0.75; nominal <i>p</i> < 0.0001). <b>Conclusions</b>: In patients with advanced NSCLC who received first-line cemiplimab-based therapy, improvements in post-baseline PROs are associated with improved OS. These results may inform endpoint selection and interpretation of future clinical trials.