{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:53:03Z","timestamp":1776315183386,"version":"3.50.1"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010355","name":"Hellenic Society of Medical Oncology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010355","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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 &lt; 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 &lt; 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 &lt; 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 &lt; 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.<\/jats:p>","DOI":"10.3390\/cancers18081239","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T10:29:08Z","timestamp":1776162548000},"page":"1239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Real-World Data on the Effectiveness of Immunotherapy on Advanced NSCLC: A Retrospective Cohort Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3317-4009","authenticated-orcid":false,"given":"Antonios","family":"Katsarolis","sequence":"first","affiliation":[{"name":"School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iliana","family":"Tapazidou-Spanoudi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5337-5688","authenticated-orcid":false,"given":"Dimitris","family":"Kugiumtzis","sequence":"additional","affiliation":[{"name":"School of Electrical and Computer Engineering, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikoleta","family":"Pastelli","sequence":"additional","affiliation":[{"name":"Department of Pathology, \u201cGeorge Papanikolaou\u201d General Hospital, 57010 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dionisios","family":"Spyratos","sequence":"additional","affiliation":[{"name":"Oncology Unit, Pulmonology Clinic, \u201cGeorge Papanikolaou\u201d General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katerina","family":"Manika","sequence":"additional","affiliation":[{"name":"Oncology Unit, Pulmonology Clinic, \u201cGeorge Papanikolaou\u201d General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasios","family":"Vagionas","sequence":"additional","affiliation":[{"name":"Oncology Department, General Hospital of Kavala, 65500 Kavala, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Lampaki","sequence":"additional","affiliation":[{"name":"Oncology Unit, Pulmonology Clinic, \u201cGeorge Papanikolaou\u201d General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Fountzilas","sequence":"additional","affiliation":[{"name":"Oncology Unit, Pulmonology Clinic, \u201cGeorge Papanikolaou\u201d General Hospital, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"},{"name":"Department of Medical Oncology, St Luke\u2019s Clinic, 55236 Thessaloniki, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,14]]},"reference":[{"key":"ref_1","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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