Longer Follow-Up Reinforces Clinical Benefit of Perioperative Durvalumab in Resectable Non-Small Cell Lung Cancer

Clinical Summary: 

• Design/Population: This double-blind, placebo-controlled trial evaluated perioperative durvalumab plus neoadjuvant platinum-based chemotherapy compared with neoadjuvant chemotherapy alone in patients with treatment-naïve, resectable stage II to IIIB (N2) non-small cell lung cancer (NSCLC).
• Key Outcomes: At the second planned interim analysis, perioperative durvalumab maintained its event-free survival benefit, with a hazard ratio of 0.69 compared with placebo. Disease-free survival also numerically favored durvalumab, while overall survival showed an early numerical improvement but remained immature and was not formally tested for statistical significance.
• Clinical Relevance: The sustained event-free survival benefit after completion of treatment strengthens the evidence supporting perioperative durvalumab as a treatment option for resectable NSCLC, while ongoing follow-up is needed to determine whether the emerging disease-free and overall survival trends translate into definitive long-term survival benefit.

Updated results from the phase 3 AEGEAN trial demonstrated that perioperative durvalumab plus neoadjuvant chemotherapy continued to improve event-free survival (EFS) compared with neoadjuvant chemotherapy alone in patients with resectable non-small cell lung cancer (NSCLC), further supporting perioperative durvalumab as a treatment option in this setting.

In this double-blind, placebo-controlled trial, 740 patients with treatment-naïve, resectable stage II to IIIB (N2) NSCLC were randomized 1:1 to receive 4 cycles of platinum-based chemotherapy plus either durvalumab (n = 366) or placebo (n = 374) once every 3 weeks before surgery, followed by 12 cycles of adjuvant durvalumab or placebo every 4 weeks. Patients with documented EGFR or ALK alterations were excluded from the modified intention-to-treat population. 

The primary end points were EFS and pathologic complete response (pCR), with disease-free survival (DFS), overall survival (OS), and safety among key secondary end points.

At a median follow-up of 25.9 months, all patients had completed or discontinued treatment. Among those who received adjuvant therapy, 68.6% of patients in the durvalumab arm and 63.7% in the placebo arm completed all planned adjuvant treatment. Disease progression was the most common reason for discontinuation. Following treatment discontinuation, 19.4% of patients in the durvalumab arm and 29.7% in the placebo arm received subsequent anticancer therapy.

The updated EFS analysis continued to favor perioperative durvalumab, with median EFS not reached in the durvalumab arm compared with 30 months in the placebo arm (hazard ratio [HR], 0.69). The treatment benefit remained generally consistent across prespecified baseline subgroups, including patients with N2 nodal disease and across planned neoadjuvant platinum regimens.

Exploratory analyses also showed an EFS benefit with durvalumab regardless of pCR status. EFS was numerically more favorable among patients who received adjuvant treatment than among those who did not, although these analyses were based on postrandomization variables and should be interpreted cautiously.

Interim DFS results also favored perioperative durvalumab (HR, 0.66; 95% confidence interval [CI], 0.47 to 0.92; P = .0137). However, the result did not cross the prespecified boundary for statistical significance at this interim analysis, and follow-up is continuing toward the final DFS analysis.

OS data remained immature. Median OS was not reached in the durvalumab arm and was 53.2 months in the placebo arm, with a numerical improvement favoring durvalumab (HR, 0.89). OS was not formally tested for statistical significance under the study’s prespecified multiple-testing procedure. Lung cancer–specific survival also favored durvalumab in an exploratory analysis (HR, 0.70).

No new safety signals were observed. During adjuvant treatment, maximum grade 3/4 adverse events occurred in 15.4% of patients receiving durvalumab and 10.6% of patients receiving placebo.

“Updated and new efficacy results continue to show a clear clinical benefit with perioperative durvalumab in patients with resectable stage IIA to IIIB NSCLC, with a manageable safety profile and no new safety signals observed,” concluded study authors. “These findings further support the addition of perioperative durvalumab to neoadjuvant chemotherapy as a new treatment option and provide additional evidence for its tolerability.”

Source: 

Heymach JV, He J, Harpole D, et al. Perioperative durvalumab for resectable non-small cell lung cancer: Updated outcomes from the phase III AEGEAN trial. J Clin Oncol. Published online: August 28, 2026. doi: 10.1200/JCO-25-02659