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AEGEAN is a phase III, international, randomized, double-blind, placebo-controlled study that investigated the efficacy of neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab in patients with resectable non-small cell lung cancer (NSCLC).  

In this trial, a total of 802 patients with stage II to IIIB NSCLC were randomly assigned to receive platinum-based chemotherapy plus durvalumab or placebo before surgery, followed by adjuvant durvalumab or placebo. This treatment was administered intravenously every 3 weeks for four cycles before surgery. Following surgery, patients received adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles.  

The randomization process considered the disease stage and the expression level of programmed death ligand 1 (PD-L1). The main objectives of the study were to assess event-free survival (the time from treatment initiation to disease progression, recurrence, or death) and pathological complete response, which was assessed centrally. 

Patients who received durvalumab showed a higher pathological complete response rate of 17.2 percent compared to 4.3 percent in the placebo group, with a notable absolute difference of 12.9 percent. Additionally, the median event-free survival was not reached in the durvalumab group, indicating a significant benefit over the control group with 25.9 months median event-free survival. 

The study highlighted that the greatest benefit of neoadjuvant durvalumab plus chemotherapy was seen in current and former smokers, aligning with findings from other immunotherapy studies. Notably, patients with stage II disease experienced a relatively larger benefit in terms of pathological complete response compared to those with stage IIIA disease. Adverse events of grade 3 or 4 were reported in a similar proportion of patients receiving durvalumab and those on placebo, emphasizing the safety profile of the treatment. 

The trial demonstrated significant improvements in event-free survival and pathological complete response rates when durvalumab was added to the treatment regimen compared to chemotherapy alone. Specifically, patients who received durvalumab showed a higher event-free survival rate at the 12-month landmark analysis compared to those who received a placebo. Moreover, the incidence of pathological complete response was notably greater with durvalumab than with a placebo, indicating a more effective response to treatment.  

The AEGEAN trial also addressed the exclusion of patients with EGFR or ALK alterations due to emerging data from other studies suggesting alternative treatment approaches for these subgroups. The results from this trial, along with findings from other recent studies like CheckMate-816, IMpower010, and KEYNOTE-091 underscored the benefits of immunotherapy in combination with chemotherapy for resectable NSCLC. However, variations in study designs and patient populations make direct comparisons challenging. 

In summary, the AEGEAN trial's significance lies in its demonstration of the positive impact of neoadjuvant durvalumab plus chemotherapy followed by adjuvant durvalumab in improving outcomes for patients with resectable NSCLC. This study represents a significant advancement in the management of NSCLC by highlighting the potential benefits of incorporating immunotherapy into perioperative treatment regimens, ultimately offering new hope and improved therapeutic options for individuals diagnosed with this challenging disease. 

References: 

Esmo. Perioperative durvalumab plus neoadjuvant chemotherapy results in greater EFS and PCR in patients with resectable NSCLC than Neoadjuvant chemotherapy alone. ESMO. Accessed March 25, 2024. https://www.esmo.org/oncology-news/perioperative-durvalumab-plus-neoadjuvant-chemotherapy-results-in-greater-efs-and-pcr-in-patients-with-resectable-nsclc-than-neoadjuvant-chemotherapy-alone. 

Heymach JV, Harpole D. Perioperative durvalumab for resectable non–small-cell ... Perioperative Durvalumab for Resectable Non–Small-Cell Lung Cancer. Accessed March 25, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2304875. 

Heymach J. Dr Heymach on Results from the AEGEAN Trial of Durvalumab in Resectable NSCLC. OncLive. April 16, 2023. Accessed March 25, 2024. https://www.onclive.com/view/dr-heymach-on-results-from-the-aegean-trial-of-durvalumab-in-resectable-nsclc. 

Imfinzi-based treatment before and after surgery reduced the risk ... Accessed March 25, 2024. https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-based-treatment-before-and-after-surgery-reduced-the-risk-of-disease-recurrence-progression-events-or-death-in-resectable-non-small-cell-lung-cancer.html.