AEGEAN trial: A phase 3 study of Neoadjuvant Durvalumab plus Chemotherapy followed by Adjuvant Durvalumab versus Neoadjuvant Chemotherapy in Patients with Resectable Non-Small Cell Lung Cancer

By Dr. Dipesh Uprety
Karmanos Cancer Institute

Four cycles of cisplatin-based adjuvant chemotherapy after surgical resection have remained the standard of care for patients with early-stage resectable non-small cell lung cancer (1). More recently, pembrolizumab and atezolizumab (for PD-L1≥1%) have been approved in the adjuvant settings, and nivolumab plus three cycles of platinum-doublet chemotherapy has been approved in the neoadjuvant setting (2-4).

At AACR 2023, the results of the AEGEAN trial were presented. This trial included patients with stage IIA-IIIB resectable non-small cell lung cancer with no EGFR/ALK mutation. Eight-hundred-two patients were randomized into four cycles of durvalumab plus platinum-doublet vs. four cycles of platinum-based chemotherapy. After surgical resection, these patients received either durvalumab or a placebo for 12 cycles. In the first planned interim analysis, the study demonstrated significant improvement in the event-free survival (EFS) in the durvalumab arm (HR 0.68, p=0.0039), with 1-year EFS being 74.3% versus 64.5%. Additionally, there was increased pCR (17.2% versus 4.3%) and MPR (33.3% versus 12.3%) in the durvalumab arm.

The AEGEAN trial is one of several trials in the peri-operative space (KEYNOTE-671, CheckMate-77T, IMPOWER-030) that have utilized neoadjuvant chemo plus immunotherapy followed by adjuvant immunotherapy. If approved by the regulatory bodies, this will be another treatment option for patients with early-stage resectable non-small cell lung cancer in the peri-operative setting. Having a similar outcome to CheckMate-816, currently, there is no compelling indication of adding one extra year of adjuvant durvalumab. Once the data has matured, we will likely know whether there is an added benefit of an additional year of adjuvant durvalumab.

References:

1. Pignon JP, Tribodet H, Scagliotti GV, Douillard JY, Shepherd FA, Stephens RJ, et al. “Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.” J Clin Oncol. 2008;26(21):3552-9.
2. Felip E, Altorki N, Zhou C, Csőszi T, Vynnychenko I, Goloborodko O, et al. “Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial.” Lancet. 2021;398(10308):1344-57.
3. O’Brien M, Paz-Ares L, Marreaud S, Dafni U, Oselin K, Havel L, et al. “Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB-IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial.” Lancet Oncol. 2022;23(10):1274-86.
4. Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. “Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer.” N Engl J Med. 2022;386(21):1973-85.
5. Heymach JV. “AEGEAN: A Phase 3 Trial of Neoadjuvant Durvalumab + Chemotherapy Followed by Adjuvant Durvalumab in Patients with Resectable NSCLC.” Presented at AACR, April 14-19, 2023.