Surgery remains the primary curative-intent treatment for eligible patients with early-stage non-small cell lung cancer (NSCLC). However, a significant number of patients experience tumour recurrence after surgery, with perioperative chemotherapy only modestly improving these results. Recently published in The New England Journal of Medicine, the results of the phase III AEGEAN trial showed that combining perioperative durvalumab plus neoadjuvant chemotherapy led to improved clinical outcomes in these patients, compared to neoadjuvant chemotherapy alone.1
Lung cancer is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) accounting for over 80% of cases. Surgery remains the primary curative-intent treatment for eligible patients with early-stage NSCLC. However, a significant number of patients experience tumour recurrence within five years after surgery (approximately 30-55%, depending on the disease stage at diagnosis). Chemotherapy administered in the neoadjuvant or adjuvant period offers only a modest 5% improvement in 5-year survival, as compared with surgery alone. The combination of immunotherapy with chemotherapy in the perioperative setting may improve the outcomes of these patients.
The phase III AEGEAN study is a randomised, double-blind, placebo-controlled, multi-centre international study assessing the activity of durvalumab plus chemotherapy administered prior to surgery, compared to placebo plus chemotherapy, in terms of pathological complete response.2
Patients with resectable NSCLC (stage II-IIIB [N2 node stage] according to the 8th edition of the AJCC Cancer Staging Manual) were randomly assigned to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every three weeks for four cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every four weeks for twelve cycles. Primary endpoints were event-free survival (EFS, defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death by any cause) and pathological complete response (pCR).
A total of 802 patients were randomly assigned to receive durvalumab (n=400) or placebo (n=402). The duration of EFS was significantly longer with durvalumab than with placebo (HR[95%CI]:0.68[0.53 to 0.88; P=0.004) at the first interim analysis. At the 12-month landmark analysis, EFS rates were reported at 73.4% vs. 64.5% in the durvalumab and placebo groups, respectively. The incidence of pCR was significantly higher with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; p<0.001). Remarkably, the EFS and PCR benefits were observed regardless of stage and PD-L1 expression. Adverse events of maximum grade 3 or 4 occurred in 42.4% of patients with durvalumab and in 43.2% of patients with placebo.
In patients with resectable NSCLC, perioperative durvalumab plus neoadjuvant chemotherapy was associated with significantly improved EFS and pCR compared to neoadjuvant chemotherapy alone, with a safety profile that was consistent with the individual agents.1
2. ClinicalTrials.gov ID NCT03800134. A Phase III, Double-blind, Placebo-controlled, Multi-center International Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Stages II and III Non-small Cell Lung Cancer (AEGEAN). Accessed on 7 November 2023.