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TOPLINE:
The EA5181 trial showed no overall survival benefit from adding concurrent durvalumab to chemoradiation compared with standard consolidation durvalumab alone in patients with stage III non-small cell lung cancer (NSCLC).
METHODOLOGY:
- Although consolidation therapy with durvalumab after definitive concurrent chemoradiotherapy improves survival in patients with unresectable stage III NSCLC, the optimal timing of immunotherapy initiation is unknown.
- Overall, 662 patients with unresectable stage III NSCLC were randomly assigned 1:1 to either concurrent durvalumab plus chemoradiation or chemoradiation alone.
- Both arms received consolidation durvalumab for 1 year after completing chemoradiation without pneumonitis or toxicity higher than grade 2.
- The primary endpoint was overall survival; secondary endpoints included progression-free survival, response rates, and toxicity patterns.
- Median follow-up reached 29.9 months, with stratification by age, sex, stage, and chemotherapy regimen.
- Most patients (82.5%) received carboplatin-paclitaxel as the platinum doublet chemotherapy backbone.
TAKEAWAY:
- Median overall survival was nearly identical: 41.5 months with concurrent durvalumab vs 39.4 months with standard care (hazard ratio [HR], 1.03; 95% CI, 0.80-1.32; P = .83).
- Progression-free survival showed no difference: 15.5 months with concurrent durvalumab vs 16.8 months with standard care (HR, 1.05; 95% CI, 0.86-1.29; P = .65).
- Response rates were similar between arms: 51.3% vs 47.1% in step 1 (P = .28) and 71.5% vs 67.1% in step 2 (P = .31).
- Safety profiles were comparable, with no significant differences in grades 3-5 adverse events or treatment discontinuation rates.
IN PRACTICE:
The findings suggest that earlier initiation of immune checkpoint inhibition does not enhance the established benefits of consolidation durvalumab.
“We did not show superiority with giving concurrent durvalumab during the course of chemoradiation therapy,” the lead investigator said during their presentation. The study establishes that the current PACIFIC trial regimen (ie, durvalumab after chemoradiotherapy) remains the standard of care for unresectable stage III NSCLC.
“If we’re looking for a benchmark with starting the PACIFIC trial regimen at the beginning of treatment, we’d say that the median survival is approximately 40 months,” the lead investigator noted.
SOURCE:
The study was led by John Varlotto, MD, Marshall University, Huntington, West Virginia. The ECOG-ACRIN Cancer Research Group conducted this phase 3 trial across multiple US institutions. Results were presented at the World Conference on Lung Cancer (WCLC) 2025 as a late-breaking abstract during the Presidential Symposium.
LIMITATIONS:
Although the trial achieved its target accrual of 662 patients, the early termination of the study may have limited the ability to detect smaller treatment effects. Moreover, while the study showed that patients receiving cisplatin-pemetrexed as chemotherapy backbone appeared to fare worse with concurrent durvalumab, the small sample sizes in this subgroup preclude definitive conclusions. In addition, the presented analysis lacks detailed radiation parameter data, which investigators plan to include in future analyses.
DISCLOSURES:
The study received funding from the National Cancer Institute of the National Institutes of Health through the ECOG-ACRIN Cancer Research Group. Varlotto reported having financial relationships with Novocure; AstraZeneca, the maker of durvalumab; and Medtronic.
