The phase 3 AEGEAN trial has demonstrated significant clinical benefits for perioperative durvalumab combined with platinum-based chemotherapy in patients with resectable non-small-cell lung cancer (NSCLC), marking a potential advancement in early-stage treatment approaches.
Trial Design and Patient Population
The AEGEAN study was a randomized, double-blind, global placebo-controlled trial that enrolled 802 participants with resectable NSCLC (stage IIA-IIIB) planned for lobectomy, sleeve resection, or bilobectomy. All patients were treatment-naïve with confirmed PD-L1 status and no documented EGFR or ALK aberrations.
Participants were randomized 1:1 to receive either durvalumab 1,500mg intravenously plus platinum-based chemotherapy or placebo plus platinum-based chemotherapy every 3 weeks for 4 cycles before surgery. Following surgical procedures, patients received durvalumab 1,500mg IV or placebo IV every 4 weeks for 12 cycles. Randomization was stratified by disease stage (stage II or III) and PD-L1 expression (≥1% or <1%).
Primary Efficacy Outcomes
With a median follow-up of 11.7 months (95% CI: 0.0-46.1), perioperative durvalumab significantly reduced the risk of event-free survival (EFS) by 32% compared to placebo (HR=0.68; 95% CI: 0.53-0.88; p=0.003902). The median EFS was not reached (95% CI: 31.9-NR) for the durvalumab arm compared to 25.9 months (95% CI: 18.9-NR) in the placebo arm. EFS benefits were consistent across patient subgroups treated with both cisplatin and carboplatin.
Pathological Response Rates
Based on an interim analysis of 402 patients, perioperative durvalumab demonstrated significantly higher pathological complete response (pCR) rates compared to placebo. The durvalumab group achieved a pCR rate of 17.2% versus 4.3% with placebo, representing a difference of 13% (95% CI: 8.7%-17.6%; p=0.000036).
The proportion of patients achieving major pathological response (MPR) was also significantly higher in the durvalumab group at 33.3% compared to 12.3% with placebo, showing a difference of 21.0% (95% CI: 15.1%-26.9%; p=0.000002).
Safety Profile
The treatment demonstrated a manageable safety profile consistent with the established safety profiles of durvalumab and chemotherapy. Grade 3/4 adverse events occurred in 42.3% of patients in the durvalumab group compared to 43.4% in the placebo group, indicating similar safety rates between treatment arms.
Clinical Significance
These results support the incorporation of immunotherapy with immune checkpoint inhibitors in perioperative settings for early-stage resectable NSCLC. The enhanced perioperative regimen, combining the benefits of neoadjuvant and adjuvant immunotherapy, demonstrates potential for improving patients' long-term clinical outcomes beyond surgery alone, which remains the first-line treatment for early-stage resectable NSCLC.
