Durvalumab lowered the risk of death by 32% in patients with non-small cell lung cancer compared to chemotherapy alone.
Perioperative durvalumab (Imfinzi; AstraZeneca) statistically and clinically improved complete response (pCR) and event-free survival (EFS) in patients with resectable early-stage (2A-3B) non-small cell lung cancer (NSCLC), meeting the primary outcomes of the AEGEAN phase 3 trial. Results from the trial were recently presented at the American Association for Cancer Research (AACR) Annual Meeting in Orlando, Florida.
“Adding durvalumab both before and after surgery has the potential to become a backbone combination approach that may alter the course of a patient’s cancer, significantly increasing the potential for cure,” said John V. Heymach, MD, PhD, professor and chair, Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, in a press release.
Durvalumab is a human monoclonal antibody that blocks the interaction between the programmed death ligand 1 (PD-L1) protein and CD80 protein to improve the body’s immune response. Investigators conducted the double-blind, multi-center, placebo-controlled global, phase 3 AEGEAN trial to evaluate durvalumab as a perioperative treatment for patients with early-stage resectable stage NSCLC, with or without PD-L1 expression.
In AEGEAN, 802 patients were randomized to receive either a 1500 mg fixed dose of durvalumab plus chemotherapy or placebo plus chemotherapy every 3 weeks for 4 cycles prior to surgery. After surgery, patients received adjuvant durvalumab or placebo every 4 weeks (for up to 12 cycles). Key secondary outcomes included major pathologic response, overall survival (OS), safety, disease-free survival (DFS), and quality of life (QoL).
At the interim analysis, perioperative durvalumab statistically and clinically improved EFS, or time from randomization to an event (i.e., tumor recurrence, progression that prevents surgery, or death) in 32% of patients compared to chemotherapy alone.
In addition, results from the final analysis suggest that durvalumab and chemotherapy prior to surgery allowed for 4-times as many patients with resectable early-stage NSCLC to achieve pCR—no viable tumor following neoadjuvant therapy— compared to neoadjuvant chemotherapy alone. The pCR rate increased to 17.2% with the addition of durvalumab compared to 4.3% with chemotherapy alone.
Durvalumab was generally well tolerated, and investigators observed no new safety signals. Grades 3 and 4 adverse events (AEs) occurred in more than 40% of participants in both trial arms. It remains the only immunotherapy in the curative-intent setting that is approved for unresectable, stage 3 NSCLC in patients whose disease has not progressed after chemoradiation therapy, and it is currently part of several clinical trials for NSCLC.
Lung cancer is the leading cause of death worldwide, with approximately 2.2 million people diagnosed each year. Although 85% of patients are diagnosed with NSCLC, most are diagnosed with advanced disease, and among the 25% to 30% who are diagnosed early enough to have surgery, many will still have recurrence.
“The AEGEAN trial shows this novel [durvalumab]-based regimen meaningfully improved outcomes in resectable lung cancer, further validating the importance of moving lung cancer diagnosis and treatment to earlier stages of disease where patients have the highest potential for cure,” said Susan Galbraith, executive vice president, Oncology R&D, AstraZeneca, in the press release.
AstraZeneca. Imfinzi-based treatment before and after surgery reduced the risk of disease recurrence, progression events or death by 32% in resectable non-small cell lung cancer in the AEGEAN Phase III trial. News Release. April 16, 2023. Accessed on April 17, 2023. 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