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

## TL;DR

This study confirms that durvalumab after chemoradiation is effective and safe for older patients with advanced lung cancer, showing long-term benefits in real-world settings.

## Contribution

The study provides real-world evidence supporting durvalumab's effectiveness and safety in older patients with unresectable stage III NSCLC.

## Key findings

- Median progression-free survival was ~43.7 months, similar to clinical trial results.
- Durvalumab was well tolerated, with grade 3-4 adverse events in 9% of patients, mostly over 65 years old.
- Smoking status significantly affected progression-free survival, with ever-smokers having longer survival.

## Abstract

The PACIFIC study results have necessitated a new standard of care for patients with non-small cell lung cancer (NSCLC). We assessed the safety and real-world efficacy of durvalumab maintenance therapy after concurrent chemoradiotherapy (cCRT) in unresectable, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable stage III NSCLC were included in the study, regardless of PD-L1 expression. Median PFS for the entire study population was ~43.7 months (approximately 3.6 years). A total of 39 patients (50%) had disease progression or death at the end of follow-up. We achieved similar PFS results to those in the PACIFIC and PACIFIC-R trials, with acceptable toxicity (grade 3 or 4 adverse events occurred in 9% of patients, almost exclusively in those over 65 years of age). Progression was more common in the younger age group than in those over 65, while deaths were more common in older patients. The results of durvalumab maintenance therapy after cCRT in LA-NSCLC in daily practice confirm the effectiveness of the therapy in real-world settings, even in older patients.

Background: 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. Methods: 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. Results: 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 (p > 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, p = 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. Conclusions: 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).