Study Finds No Survival Benefit of Concurrent Durvalumab with Chemoradiotherapy in Unresectable Stage III NSCLC

Recent research presented at the 2025 World Conference on Lung Cancer by the International Association for the Study of Lung Cancer indicates that adding durvalumab concurrently with chemoradiotherapy (CRT) does not lead to improved overall survival in patients with unresectable stage III non-small cell lung cancer (NSCLC). The Phase III EA5181 trial involved 662 patients with untreated unresectable stage IIIA-C NSCLC or mediastinal node recurrence after surgery, who were randomly assigned to either receive durvalumab concurrently with chemotherapy and radiotherapy (Arm A) or to undergo CRT alone (Arm B). Both groups proceeded to a year of durvalumab consolidation if they completed CRT without progression or severe toxicity.

The results showed median overall survival was nearly identical between the two groups: 41.5 months for the concurrent treatment arm and 39.4 months for the consolidation-only arm, with no statistically significant difference (p=0.83). Progression-free survival was also similar, at 15.5 versus 16.8 months, respectively. Importantly, there were no significant differences in objective response rates, patterns of failure, or adverse effects between the two approaches.

Dr. John Varlotto from Marshall University explained that the addition of durvalumab during CRT did not enhance survival outcomes, reaffirming that initiating durvalumab as consolidation therapy after CRT remains the best practice. The study also identified that factors such as ECOG performance status, adenocarcinoma histology, and DLCO over 80% were linked to better survival outcomes, while prior thoracic surgery correlated with improved progression-free survival.

This study underscores that current treatment protocols focusing on sequencing durvalumab after chemoradiotherapy are optimal for managing unresectable stage III NSCLC, providing valuable insights for clinicians in optimizing therapeutic strategies.