Concurrent Durvalumab Plus Chemo/RT Does Not Improve Efficacy in Stage III NSCLC

For patients with unresectable stage III NSCLC, concurrent durvalumab with chemotherapy/radiation did not show an efficacy improvement.

Efficacy was not improved with concomitant durvalumab (Imfinzi) during chemotherapy and radiation (RT) for patients with stage III unresectable non-small cell lung cancer (NSCLC), according to results from the phase 3 EA5181 trial presented at the 2025 World Conference on Lung Cancer.

In the durvalumab arm, the median overall survival (OS) was 41.5 months (95% CI, 34.4-not reached [NR]) vs 39.4 months (95% CI, 33.4-NR) for patients in the chemotherapy/RT arm (HR, 1.03; 95% CI, 0.80-1.32; P = .83). The median progression-free survival (PFS) was 15.5 months in the durvalumab arm (95% CI, 13.9-22.1) vs 16.4 months (95% CI, 12.0-20.2) in the chemotherapy/RT arm (HR, 1.05; 95% CI, 0.86-1.29; P = .65).

“In patients with unresectable, stage III [NSCLC], the addition of concomitant durvalumab during the course of chemotherapy/radiation did not improve OS, did not improve PFS, did not change the recurrence patterns or ORRs [overall response rates], and did not increase toxicity,” John M. Varlotto, MD, professor and chief of Radiation Oncology at Marshall Health, stated during the presentation.

Patients were randomly assigned 1:1 to receive either platinum doublet durvalumab at 750 mg every 2 weeks plus 3 concurrent rounds of RT at 60 Gy or platinum doublet chemotherapy with concurrent RT at 60 Gy. Patients could then transition to consolidation durvalumab at 1500 mg every 4 weeks for 1 year from the end of chemotherapy/RT. This transition could occur within 2 weeks, but may be delayed up to 45 days, depending on whether patients’ toxicities are not grade 2 or less.

Patients were stratified by planned chemotherapy, age, sex, and disease stage. Patients were eligible for treatment if they had unresectable stage IIIA to C NSCLC and had an ECOG performance status of 0 to 1.The primary end point was OS, with secondary end points being PFS, toxicity, ORRs, and recurrence patterns.

A total of 662 patients were randomly assigned to either arm. Varlotto noted the study had an 82% power to detect a 25% reduction in the OS HR rate of 0.01631 to 0.01223, and a 1-sided alpha level of 0.025.

The median follow-up was 29.9 months (95% CI, 28.4-33.1). In the durvalumab arm, 335 patients were enrolled, with 305 completing treatment, and 277 moving on to consolidation. In the chemotherapy/RT arm, 327 patients were enrolled, 300 completed treatment, and 277 moved on to consolidation.

Across both arms, 60.6% of patients were male, the median age was 67.1 years (range, 37.6-89.4), and 50.6% of patients had stage IIIA disease. Additionally, 48.7% of patients had adenocarcinoma, 53.3% were former smokers, and 82.5% were given carboplatin/paclitaxel.

A total of 45.4% of patients had experienced disease progression in the durvalumab arm, and 44.0% had it in the chemotherapy/RT arm. Local recurrence was noted in 55.9% vs 49.6% (P = .34), and radiation in-field recurrences were observed in 28.6% vs 28.4% (P = .98).

Prior to consolidation, the ORR was 51.3% in the durvalumab arm and 47.1% in the chemotherapy/RT arm (P = .28), while in consolidation, the ORR was 71.5% vs 67.1% (P = .31). In both arms, the median number of consolidative cycles of durvalumab was 10.

In the durvalumab arm, adverse effects (AEs) of any grade occurred in 99.1% vs 98.7% in the chemotherapy/RT arm, while grade 3/4 AEs were noted in 67.7% vs 62.2%., Serious AEs were observed in 3.6% vs 3.5%, and AEs leading to treatment discontinuation occurred in 19.0% vs 16.5%.

The most common grade 3 to 5 treatment-related AEs in the durvalumab and chemotherapy/RT arms were lymphocyte count decrease (50% vs 45%), white blood cell count decrease (22% vs 27%), esophagitis (21% vs 27%), neutrophil count decrease (16% vs 14%), and pneumonitis (12% vs 5%).

Reference

Varlotto JM, Xie Y, Pennell N, et al. ECOG-ACRIN EA5181: phase 3 trial of concurrent and consolidative durvalumab vs consolidation durvalumab alone for unresectable stage III NSCLC. Presented at the 2025 World Conference on Lung Cancer; Barcelona, Spain; September 6-9, 2025. Abstract PL-3.04.