As reported in The New England Journal of Medicine by John V. Heymach, MD, PhD, and colleagues, the phase III AEGEAN trial has shown that perioperative durvalumab improved event-free survival and pathologic complete response (pCR) rate in patients with resectable non–small cell lung cancer (NSCLC).

John V. Heymach, MD, PhD

Study Details

In the double-blind trial, 802 patients with stage II to IIIB disease enrolled from sites in 28 countries between January 2019 and April 2022 were randomly assigned to receive neoadjuvant platinum-based chemotherapy plus durvalumab at 1,500 mg (n = 400) or placebo (n = 402) every 3 weeks for four cycles; patients then received adjuvant durvalumab or placebo every 4 weeks for 12 cycles. The primary endpoints were event-free survival and pCR rate in the modified intent-to-treat population, consisting of 366 patients in the durvalumab group and 374 in the control group who did not have documented EGFR or ALK alterations.

Efficacy Outcomes

At interim analysis, median event-free survival was not reached (95% confidence interval [CI] = 31.9 months to not reached) in the durvalumab group vs 25.9 months (95% CI = 18.9 months to not reached) in the control group (stratified hazard ratio [HR] = 0.68, 95% CI = 0.53–0.88, P = .004). Rates at 12 and 24 months were 73.4% vs 64.5% and 63.3% vs 52.4%, respectively. Benefit of durvalumab was observed irrespective of disease stage (HRs = 0.76, 0.57, and 0.83 for stage II, IIIA, and IIIB, respectively) and tumor cell PD-L1 expression (HRs = 0.76, 0.70, and 0.60 for expression < 1%, 1%–49%, and ≥ 50%, respectively).

At final analysis, which was not statistically analyzed, pCR was achieved in 17.2% of patients in the durvalumab group vs 4.3% of the control group (difference = 13.0 percentage points, 95% CI = 8.7–17.6 percentage points). Statistical significance of the durvalumab benefit (P < .001) was observed at interim analysis of data from 402 patients. The pCR benefit of durvalumab was observed irrespective of disease stage and PD-L1 expression.

Adverse Events

Among all patients in the trial, grade 3 or 4 adverse events occurred in 42.4% of the durvalumab group vs 43.2% of the control group, including 32.2% vs 36.2% during neoadjuvant treatment. Serious adverse events occurred in 37.7% vs 31.4% of patients. Adverse events led to discontinuation of durvalumab in 12.0% of patients and discontinuation of placebo in 6.0% of patients. Adverse events considered at least possibly related to treatment led to death in seven patients (1.7%) in the durvalumab group (interstitial lung disease in two, and immune-mediated lung disease, pneumonitis, hemoptysis, myocarditis, and decreased appetite in one each) and in two patients (0.5%) in the control group (pneumonia and infection in one each).

The investigators concluded, “In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly greater event-free survival and pCR than neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents.”

Dr. Heymach, of the Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, is the corresponding author for The New England Journal of Medicine article.

Disclosure: The study was funded by AstraZeneca. For full disclosures of the study authors, visit nejm.org.