Therapy Line and Associated Predictors of Response to PD-1/PD-L1-Inhibitor Monotherapy in Advanced Non-small-Cell Lung Cancer: A Retrospective Bi-centric Cohort Study

Background Evidence on PD-1/PD-L1-directed immune checkpoint inhibitor (ICI) therapy for advanced non-small-cell lung cancer (NSCLC) is mainly based on clinical trials in first- or second-line settings. Objective We aimed to investigate response and prognostic factors with special regard to third- or later-line therapy. Patients and Methods We retrospectively analyzed all patients who had received ICI monotherapy with nivolumab, pembrolizumab, or atezolizumab for advanced NSCLC. Computed tomography evaluations were analyzed using response evaluation criteria in solid tumors (RECIST, version 1.1). KaplanMeier analyses were conducted to calculate progression-free (PFS) and overall (OS) survival; the impact of influencing variables was evaluated using uni- and multivariate Cox-regression analyses. Results Among 153 patients (59% men, mean age 66 years), median PFS was 4 months [mo; 95% confidence interval (95% CI) 35], OS was 13 mo (1017), and objective response rate (ORR) was 22%. Therapy line 3 was associated with significantly inferior PFS (p = 0.003) and OS (p = 0.001). In first-line therapy PFS, OS, and ORR were 7 mo (311), 17 mo [9not evaluable (n.e.)], and 36%; in second-line 4 mo (37), 18 mo (13n.e.) and 19%, and in third-line 2 mo (13), 9 mo (412), and 13%. PFS was significantly influenced by PD-L1 expression in first-line therapy (p = 0.006). In third-line patients, Eastern Cooperative Oncology Group (ECOG) performance status significantly affected PFS and OS (both p < 0.001). Conclusions Third- or later-line single-agent anti-PD-1/PD-L1 therapy is less efficacious as compared to first- and second-line treatment. In that setting, ECOG performance status predominates known predictors like PD-L1 expression or presence of an alteration in EGFR or ALK. Key Points Compared to first- or second-line of treatment, NSCLC patients who had received PD-1/PD-L1-directed immune checkpoint inhibitor monotherapy in line three had significantly inferior PFS and OS. In multivariate analyses among all patients, PFS was significantly influenced by PD-L1 expression and ECOG performance status, for OS only therapy line was shown to have a significant impact. In first-line treated patients, PFS was significantly influenced by PD-L1 expression, while there were no significant multivariate findings for first-line OS and second-line PFS/OS. In third-line patients, ECOG performance status significantly affected PFS and OS. (VLID)4641962