Durvalumab Improves Event-Free Survival in Resectable Non–Small Cell Lung Cancer

Results from the AEGEAN phase 3 trial found that durvalumab (Imfinzi; AstraZeneca)-based treatment before and after surgery for resectable early-stage non–small cell lung cancer (NSCLC) significantly increased the time that patients lived without recurrence or progression events.

Results from the final pathologic complete response and major pathologic response analyses were consistent with previously announced positive results. The trial will continue to assess key secondary endpoints, including disease-free survival and overall survival.

AEGEAN is a randomized, double-blind, multi-center, placebo-controlled global trial evaluating durvalumab as perioperative treatment for patients with resectable stage 2A-3B NSCLC, irrespective of programmed death-ligand 1 (PD-L1) expression. Perioperative therapy includes treatment before and after surgery.

In the trial, 802 patients were randomized to receive a 1500 mg fixed dose of durvalumab plus chemotherapy or placebo plus chemotherapy every 3 weeks for 4 cycles prior to surgery, followed by durvalumab or placebo every 4 weeks for up to 12 cycles after surgery. Patients with known EGFR or ALK genomic tumor aberrations were excluded from the primary efficacy analyses.

The primary endpoints were pathologic complete response, defined as no viable tumor in the resection specimen following neoadjuvant therapy, and event-free survival, defined as the time from randomization to an event such as tumor recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were major pathologic response, disease-free survival, overall survival, safety, and quality of life.

“Treating patients early with durvalumab both before and after surgery delivers a significant and clinically meaningful benefit in resectable non–small cell lung cancer, where new options are urgently needed to offer patients the best chance of long-term survival,” said John V. Heymach, MD, PhD, professor and chair of Thoracic/Head and Neck Medical Oncology at the University of Texas MD Anderson Cancer Center, in a press release. “The AEGEAN results provide compelling evidence that this novel durvalumab regimen can drive improved outcomes in this curative-intent setting.”

Each year, there are an estimated 2.2 million diagnoses of lung cancer globally, 80% to 85% of which are NSCLC. Approximately 25% to 30% of all patients with NSCLC are diagnosed early enough to have surgery with curative intent, although only around 56% to 65% of patients with stage 2 disease will survive for 5 years. This decreases to 41% for patients with stage 3A disease and 24% for patients with stage 3B disease, reflecting a high unmet medical need.

Durvalumab was well-tolerated in the AEGEAN trial and no new safety concerns were observed in the neoadjuvant and adjuvant settings. Additionally, adding durvalumab to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not increase complications or adverse events, or comprise patients’ ability to undergo surgery versus chemotherapy alone.

“Patients with resectable non–small cell lung cancer face unacceptably high rates of recurrence, despite treatment with chemotherapy and surgery,” said Susan Galbraith, executive vice president of Oncology Research and Development at AstraZeneca, in the press release. “We have shown that adding Imfinzi both before and after surgery significantly increased the time patients live without recurrence or progression events. We will continue to follow patients for overall survival.”

REFERENCE

Imfinzi significantly improved event-free survival in AEGEAN phase III trial for patients with resectable non–small cell lung cancer. News release. AstraZeneca; March 9, 2023. Accessed March 9, 2023. https://www.astrazeneca.com/media-centre/press-releases/2023/imfinzi-improved-efs-in-resectable-lung-cancer.html