Findings from the phase 3 EA5181 trial indicate that the combination of durvalumab (Imfinzi) with chemoradiotherapy does not enhance survival outcomes for patients with unresectable stage III non-small cell lung cancer (NSCLC). The results were presented at the International Association for the Study of Lung Cancer conference held in Barcelona, Spain, from September 6-9, 2025.
In the trial, patients receiving concurrent durvalumab and chemoradiation exhibited a median overall survival (OS) of 41.5 months compared to 39.4 months for those undergoing chemoradiation alone. The hazard ratio was calculated at 1.03 (95% CI, 0.80-1.32; P = .83), indicating no significant survival advantage. Similarly, the median progression-free survival (PFS) was 15.5 months for the durvalumab group versus 16.4 months for the chemoradiation arm (HR, 1.05; 95% CI, 0.86-1.29; P = .65).
During the presentation, John M. Varlotto, MD, Chief of Radiation Oncology at Marshall Health, stated, “In patients with unresectable, stage III NSCLC, the addition of concomitant durvalumab during the course of chemotherapy and radiation did not improve OS, PFS, recurrence patterns, overall response rates, or increase toxicity.”
The trial involved 662 patients who were randomly assigned in a 1:1 ratio to receive either the combination of durvalumab at 750 mg every two weeks along with three rounds of radiotherapy at 60 Gy or platinum doublet chemotherapy with concurrent radiotherapy at the same dosage. After completing chemoradiation, patients could transition to consolidation durvalumab at 1500 mg every four weeks for one year, contingent upon their toxicity levels.
Patient eligibility criteria included unresectable stage IIIA to C NSCLC and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. The primary endpoint of the study was OS, while secondary endpoints included PFS, toxicity, overall response rates (ORRs), and recurrence patterns.
Of the total participants, 335 patients were in the durvalumab arm, with 305 completing treatment and 277 proceeding to consolidation. In the chemoradiation arm, 327 patients were enrolled, with 300 completing treatment and also 277 moving on to consolidation. Notably, 60.6% of the participants were male, with a median age of 67.1 years (range, 37.6-89.4).
The study also revealed that 48.7% of patients had adenocarcinoma, and 53.3% were former smokers, with 82.5% receiving a carboplatin/paclitaxel regimen. Disease progression occurred in 45.4% of patients in the durvalumab arm, compared to 44.0% in the chemoradiation group. Local recurrence rates were 55.9% versus 49.6% (P = .34), and radiation field recurrences were similar at 28.6% and 28.4% (P = .98).
In terms of treatment response, the overall response rate prior to consolidation was 51.3% in the durvalumab arm versus 47.1% in the chemoradiation arm (P = .28). Following consolidation, the ORR was 71.5% compared to 67.1% (P = .31). Both treatment groups had a median of 10 cycles of consolidative durvalumab.
The adverse effects (AEs) profile showed that any grade AEs occurred in 99.1% of patients in the durvalumab arm compared to 98.7% in the chemoradiation arm. Serious AEs were reported in 3.6% versus 3.5% of patients, and AEs leading to treatment discontinuation were seen in 19.0% versus 16.5% of patients, respectively.
The most common grade 3 to 5 treatment-related AEs included decreases in lymphocyte counts (50% durvalumab vs 45% chemoradiation), white blood cell counts (22% vs 27%), and esophagitis (21% vs 27%).
Overall, the findings from the EA5181 trial indicate that the concurrent use of durvalumab with chemoradiotherapy does not provide a survival advantage for patients with unresectable stage III NSCLC. This research contributes vital information to ongoing discussions regarding treatment strategies for this challenging patient population.
