Dr Harpole on the Design of an Exploratory Analysis of the AEGEAN Trial in NSCLC

David Harpole, MD, George Barth Geller Distinguished Professor for Research in Cancer, professor, surgery, pathology, member, Duke Cancer Institute, discusses on the rationale and design of an exploratory analysis of the phase 3 AEGEAN trial (NCT03800134) in patients with EGFR-mutated non–small cell lung cancer (NSCLC), which he presented at the 2023 IASLC World Conference on Lung Cancer.

This trial was designed approximately 5 years ago, prior to any indication that upfront immunotherapy played a role in the treatment of patients with NSCLC in a trimodal approach, Harpole says. Investigators had obtained data from patients with advanced lung cancer thatindicated that the use of immunotherapy in conjunction with chemotherapy or as a standalone treatment was advantageous, Harpole explains. Consequently, the AEGEAN trial was devised to investigate the efficacy of durvalumab (Imfinzi) alongside platinum-based chemotherapy in patients with locally advanced NSCLC who were potential candidates for surgery, Harpole adds. Notably, Harpole says that the primary end point of the trial was to assess whether this approach could enhance patient downstaging and overall outcomes.

Traditionally, when administering platinum-based chemotherapy alone as the initial treatment for patients with locally advanced NSCLC followed by surgery, the complete response rate was approximately 4% to 5%, he expands. Additionally, the rate of downstaging of affected nodes ranged from 15% to 20%, Harpole notes, saying that therefore, the improvements observed with this approach were relatively modest. Overall, AEGEAN investigators held optimism that by combining immunotherapy with chemotherapy, they could achieve a more significant increase in patient outcomes.

The trial's design differed from the designs of other large trials. This approach was grounded in the knowledge that durvalumab, when administered after chemoradiation in patients with locally advanced NSCLC, extended the period of consolidative treatment, Harpole continues. This trial's design involved offering chemotherapy and durvalumab upfront, randomized against chemotherapy alone, and providing durvalumab or placebo after resection for 1 year, he notes. AEGEAN assessed the potential benefits of chemotherapy before surgery and the use of immunotherapy before and after surgery, Harpole concludes.