Background: Immuno-oncological (IO) therapies such as PD-1 and PD-L1 antibodies have been introduced in the treatment of advanced non-small cell lung cancer (NSCLC) since 2015 based on randomized trials showing unprecedented advantages in overall survival (OS) with hazard ratios (HRs) between 0.5 and 0.7. The impact of these treatments on OS in routine clinical practice and the role of tumor mass have not been studied. Methods: 557 consecutive patients with inoperable stage III or stage IV NSCLC diagnosed in our certified lung cancer center from 2006 to 2018 were included if they had received at least one line of systemic treatment. OS of immuno-oncologically treated patients (IO patients, n = 144) who received treatment with a PD-1 antibody (nivolumab [n = 77] or pembrolizumab [n = 51]) or a PD-L1 antibody (atezolizumab [n = 4] or durvalumab [n = 12]) was compared to historic controls treated before availability of IO treatment (n = 413) using case-control analysis. IO patients and historic controls were individually matched for stage, performance state, histology, smoking status, gender, age, and initial treatment mode (palliative vs. definitive radio-chemotherapy). Results: Case-control analysis of 91 matched pairs showed significantly longer OS in IO patients compared to historic controls (21.2 vs. 10.9 months, HR 0.526, CI 0.373–0.723). The benefit was more pronounced in patients with lower tumor stage (HR 0.48 [stage III], 0.40 [IVA], 0.63 [IVB]) or smaller tumor size (HR 0.38 [RECIST ≤57 mm], 0.40 [RECIST 58–94 mm], 0.59 [RECIST 95–141 mm], 0.75 [RECIST ≥142 mm]). Conclusions: IO patients showed significant benefit in OS with HRs comparable to those reported in phase III trials. The benefit tended to be greater in patients with lower tumor mass.
