A Real-World, Single-Center, Observational Retrospective Experience of Durvalumab Treatment After Concomitant Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer

<b>Background</b>: Non-small cell lung cancer (NSCLC) constitutes about 80-85% of lung cancers, and ~60-70% of NSCLC patients are diagnosed at an advanced stage of the disease. Concurrent chemoradiotherapy (cCRT) followed by consolidation durvalumab has become the standard of care for unresectable stage III NSCLC, following the phase III PACIFIC trial, which demonstrated significantly improved progression-free survival (PFS) and overall survival (OS) with durvalumab. <b>Methods</b>: We conducted a single-center retrospective study with unresectable stage III NSCLC patients who received cCRT between January 2021 and December 2025 at the Białystok Oncology Center (Poland). Patients with an ECOG performance status of 0-1 and no disease progression (PD) after cCRT were treated with durvalumab consolidation up to 12 months or until PD or unacceptable toxicity. The clinical outcomes and treatment tolerance were analyzed. <b>Results</b>: Out of 94 cCRT-treated patients (pts), 78 received durvalumab consolidation therapy. The median age of the pts was 66.5 years; 64.1% pts were >65 years old. Squamous carcinoma was the predominant histology (56.4%). The median time from cCRT completion to durvalumab initiation was 45 days (range: 15-85). A majority (57.7%) of patients completed the full 12 months of durvalumab. With a median follow-up of 40 months, the median PFS was ~1224 days (40.2 months). At 3 years, PFS was 52.8%. There were no significant differences in PFS by age (<65 vs. ≥65 years), HR:0.65, clinical stage (IIIA vs. IIIB/IIIC) HR:1.01, histology (squamous vs. non-squamous carcinoma), HR:0.76; sex HR:0.6, ECOG 0 vs. 1 HR:0.82; or initiation of durvalumab ≤42 vs. >42 days after cCRT, HR:0.62 (<i>p</i> > 0.05 for all). The sole factor significantly affecting PFS was smoking status: ever-smokers had a longer PFS than never-smokers (median ~46 months vs. ~21 months, HR:2.11, <i>p</i> = 0.04). Durvalumab consolidation was generally well tolerated. Grade 3-4 adverse events (mainly pneumonitis and esophagitis) leading to permanent durvalumab discontinuation occurred in 7 patients (9%), almost all over 65 years old. <b>Conclusions</b>: Real-world data from our single-center study confirm that consolidation durvalumab therapy after cCRT provides substantial clinical benefit in unresectable stage III NSCLC, even in older patients. The PFS and safety outcomes in our cohort, which had a higher proportion of elderly and locally advanced cases, were comparable with those reported in clinical trials (PACIFIC) and observational studies (PACIFIC-R), underscoring the effectiveness and tolerability of this approach in routine practice. We acknowledge the limitations of the retrospective design and sample size, but our findings support the use of cCRT followed by durvalumab in eligible stage III NSCLC patients and highlight the need for further research on optimizing outcomes (e.g., the impact of smoking and other biomarkers).