Predictive Factors Associated with Long-Term Response to Combination Immunotherapy in Patients with Untreated Advanced Non-Small-Cell Lung Cancer: A Multicenter Retrospective Study

Abstract

<b><i>Introduction:</i></b> Combination immunotherapy is widely used in clinical practice as the first-line treatment for advanced non-small-cell lung cancer (NSCLC). However, predictive factors associated with long-term response to combination immunotherapy have not been well investigated. Herein, we compared the clinical findings, including systemic inflammatory nutritional biomarkers, between responders and nonresponders to combination immunotherapy. In addition, we investigated the predictive factors associated with long-term response to combination immunotherapy. <b><i>Methods:</i></b> This study included a total of 112 previously untreated advanced NSCLC patients who received combination immunotherapy at eight institutions in Nagano prefecture between December 2018 and April 2021. The responders were defined as those who achieved progression-free survival for 9 months or longer with combined immunotherapy. We evaluated predictive factors associated with long-term response, and the favorable prognostic predictors associated with overall survival (OS) using statistical analyses. <b><i>Results:</i></b> The responder and nonresponder groups included 54 and 58 patients, respectively. Compared with the nonresponder group, the responder group had significantly younger age (<i>p</i> = 0.046), higher prognostic nutritional index (44.8 vs. 40.7, <i>p</i> = 0.010), lower C-reactive protein/albumin ratio (CAR) (0.17 vs. 0.67, <i>p</i> = 0.001), and a higher rate of complete plus partial response (83.3% vs. 34.5%, <i>p</i> < 0.001). The area under the curve and optimal cut-off value for CAR were 0.691 and 0.215, respectively. The CAR and best objective response were identified as independent favorable prognostic predictors associated with OS in the multivariate analyses. <b><i>Conclusion:</i></b> The CAR and best objective response were suggested to be useful predictors of long-term response in NSCLC patients who received combination immunotherapy.