The predictive utility of patient-reported outcomes and performance status for survival in metastatic lung cancer patients treated with chemoimmunotherapy

Background: Atezolizumab, an immune checkpoint inhibitor, in combination with chemotherapy (chemoimmunotherapy) has become a first-line treatment option for metastatic non-small cell lung cancer (NSCLC). Patient-reported outcomes (PROs) are self-reported measures that have shown promise in their predictive value for survival. However, there have been no studies that have assessed the prognostic performance of PROs in an advanced NSCLC cohort initiating first-line atezolizumab based chemoimmunotherapy. Methods: This study used individual-participant data (IPD) from the IMpower130, IMpower131 and IMpower150 clinical trials. Cox proportional hazards regression was utilized to determine the association between pre-treatment PROs with overall survival (OS) and progression free survival (PFS). The prediction performance of PROs was assessed using the C-statistic. For the PRO measure identified as the most predictive of survival, an exploratory analysis comparing the predictive performance against Eastern Cooperative Oncology Group Performance Status (ECOG-PS) was conducted. Results: Patient-reported physical function, fatigue, appetite loss, pain, role function, global health status, social function, dyspnoea, constipation, nausea and vomiting, insomnia, emotional function, cognitive function, and financial difficulty were statistically associated with OS (P<0.05). Physical function (c=0.62), fatigue (c=0.61), and appetite loss (c=0.60) were the most predictive variables for OS. Patient-reported physical function (c=0.60) also had higher predictive performance than physician-defined ECOG-PS (c=0.57). Conclusions: In patients with advanced NSCLC who received first line atezolizumab based therapy, pre-treatment PROs were prognostic for survival outcomes. Patient-reported physical function had higher predictive performance compared to physician-defined ECOG-PS. These results suggest PROs have significant worth in clinical practice and research trials of ICIs as a stratification factors.