Trial Design & Participants
- AEGEAN (NCT03800134) is a randomized, double-blind, placebo-controlled, multi-center global trial involving 802 treatment-naïve patients with resectable NSCLC (stages IIA–IIIB; tumors ≥4 cm and/or node-positive), excluding those with EGFR or ALK alterations. Participants were randomized (1:1) to receive:
- Durvalumab (Imfinzi) + platinum-based chemotherapy, followed by adjuvant durvalumab, or
- Placebo + chemotherapy, followed by adjuvant placebo
Treatment included four cycles of neoadjuvant therapy, surgery, and up to 12 cycles of adjuvant therapy.
Key Efficacy Outcomes
- Event-Free Survival (EFS):
- At interim analysis (median follow-up ~11.7 months):
- Durvalumab arm: median EFS not reached (lower bound 31.9 months)
- Placebo arm: median EFS 25.9 months
- Hazard Ratio: 0.68 (95% CI: 0.53–0.88; P ≈ 0.004), reflecting a 32% reduction in the risk of recurrence, progression, or death
- At interim analysis (median follow-up ~11.7 months):
- Pathologic Complete Response (pCR):
- 17.2% in the durvalumab group vs 4.3% with placebo—a 13% absolute improvement (P < 0.001)
- Benefit across subgroups: Consistent efficacy seen regardless of disease stage (II vs III), histology, and PD-L1 expression levels (<1%, 1–49%, ≥50%)
Safety & Surgical Feasibility
- Grade 3–4 adverse events were comparable between groups (~42%), indicating a manageable safety profile
- Serious adverse events occurred in 37.7% (durvalumab) vs 31.4% (placebo). Treatment-related discontinuation of durvalumab occurred in roughly 12% of patients, compared to 6% with placebo.
- Treatment-related deaths: Seven (1.7%) in the durvalumab arm (causes included interstitial lung disease, pneumonitis, myocarditis, hemoptysis, and decreased appetite) vs two (0.5%) in the placebo group
- Surgery completion was preserved: about 77.6% (durvalumab arm) vs 76.7% (control) proceeded to surgery, showing that adding durvalumab did not compromise surgical feasibility
Regulatory Milestone
- Based on these positive results, in August 2024, the FDA approved durvalumab plus chemotherapy as neoadjuvant therapy, followed by adjuvant durvalumab, for adult patients with resectable NSCLC (tumors ≥4 cm and/or node-positive) without EGFR or ALK mutations