Real-World Data on the Effectiveness of Immunotherapy on Advanced NSCLC: A Retrospective Cohort Study

Background/Objectives: The aim of the study was to evaluate the real-world effectiveness of immunotherapy compared to chemotherapy in advanced non-small-cell lung cancer (NSCLC) and assess molecular profiling patterns in a large Greek cohort. Methods: This was a retrospective study of patients with advanced NSCLC from three oncology centers. Clinical, pathological, and/or molecular data were collected from the patient medical records. The primary endpoint was overall survival (OS). Results: Overall, 684 patients with advanced NSCLC were included; median age 67 years (range, 33 to 89). More than half of the patients (406, 59.4%) had been diagnosed with de novo metastatic disease. Overall, 289 of 684 (42.3%) patients underwent tumor molecular profiling. Immunotherapy use, with or without chemotherapy, in the first-line setting increased significantly over time (p < 0.001). Among 610 patients eligible for outcome analysis, immunotherapy at any line of treatment was associated with increased OS compared to chemotherapy alone (17.5 vs. 8.6 months; HR: 0.51, 95% CI: 0.42, 0.61; p < 0.001). The results remained consistent with the primary analysis as well as the landmark analysis using a 3-month cutoff to account for the immortal-time bias. Furthermore, time to next treatment (TTNT) was significantly longer with immunotherapy use in both first- and second-line treatment (TTNT1: 10.0 vs. 6.8 months, HR: 0.45, 95% CI: 0.34, 0.58; p < 0.001; TTNT2: 6.7 vs. 5.9 months, HR: 0.59, 95% CI: 0.40, 0.87; p = 0.009). Immunotherapy use remained an independent predictor of improved survival (HR: 0.50, 95% CI: 0.40, 0.63; p < 0.001). Conclusions: Immunotherapy, with or without chemotherapy, significantly improved clinical outcomes compared to chemotherapy alone in a real-world cohort of patients with advanced NSCLC. While molecular testing rates increased significantly over the study, only a minority of patients underwent PD-L1 testing, while broad molecular profiling was also incomplete, limiting the interpretation of treatment effects. Improvements to guarantee the universal molecular testing of patients with NSCLC are warranted.