NEWS & PERSPECTIVE
Perioperative durvalumab plus neoadjuvant chemotherapy shows benefits in resectable NSCLC
Although surgery remains the first-line treatment for patients with early-stage resectable non-small-cell lung cancer (NSCLC), recent evidence has shown that the incorporation of immunotherapy with immune checkpoint inhibitors, such as programmed cell death-1 (PD-1) or programmed cell death ligand-1 (PD-L1), demonstrated benefits in the perioperative settings.1 It is believed that the enhanced perioperative regimens, by combining the benefits of neoadjuvant and adjuvant immunotherapy, could further improve patients’ long-term clinical outcomes.1
The AEGEAN was a phase 3, randomized and double-blind, global placebo-controlled study that included 802 participants with a resectable NSCLC (stage IIA-IIIB) who were planned for a lobectomy, sleeve resection, or bilobectomy.1 These patients were treatment-naïve and had a confirmed PD-L1 status, without any documented estimated glomerular filtration rate (EGFR) or anaplastic lymphoma kinase (ALK) aberrations.1 Participants were randomized 1:1 to receive durvalumab 1,500mg intravenously (IV) + platinum-based chemotherapy or placebo add space before + platinum-based chemotherapy group every 3 weeks (Q3W) for 4 cycles before surgery.1 After surgical procedures were performed, patients were administered durvalumab 1,500mg IV or placebo IV Q4W for 12 cycles.1 Randomization was stratified according to their disease stage (stage II or III) and PD-L1 expression (≥1% or <1%).1 The primary outcomes included pathological complete response (pCR) assessed by the central lab as per the International Association for the Study of Lung Cancer (IASLC) 2020 criteria, and event-free survival (EFS) as per the blinded independent central review (BICR).1 The secondary outcomes included the major pathological response (MPR) assessed by the central lab as per the IASLC 2020 criteria, disease-free survival (DFS) using, and overall survival (OS).1
With a median follow-up of 11.7 months (95% CI: 0.0-46.1), the study showed that perioperative durvalumab significantly reducedthe risk of EFS by 32% in patients with resectable NSCLC vs. placebo(HR=0.68; 95% CI: 0.53-0.88; p=0.003902).1 The median EFS was not reached (NR) (95% CI: 31.9-NR) for the durvalumab arm and was 25.9 months (95% CI: 18.9-NR) in the placebo arm.1 EFS benefits are consistent across patient subgroups treated with cisplatin and carboplatin.1 On the other hand, based on an interim analysis (n=402), perioperative durvalumab also demonstrated a significantly higher CR rate of 17.2% vs. 4.3% with placebo, with a difference of13% (95% CI: 8.7%-17.6%; p=0.000036).1 The proportion of patients achieving MPR was also significantly higher in the durvalumab group (33.3%) when compared with placebo (12.3%), with a difference of 21.0% (95% CI: 15.1%-26.9%; p=0.000002).1
with gradeThe rates of adverse events (AEs) were similar in both groups, withgrade 3/4 AEs occurring in 42.3% and 43.4% of patients in the durvalumab and placebo groups, respectively.1 Overall, perioperative. durvalumab plus neoadjuvant CT demonstrated a manageable safety profile which was consistent with the established safety profile of durvalumab and CT.1
In summary, the AEGEAN study has shown that perioperative durvalumab with neoadjuvant CT significantly improves pCR andEFS in patients with resectable NSCLC as compared to neoadjuvant CT alone, providing a potential novel treatment option for such patients to improve treatment outcomes.1
