Patients with treatment-naïve resectable non-small cell lung cancer (NSCLC) who received neoadjuvant durvalumab (Imfinzi) plus chemotherapy and adjuvant durvalumab monotherapy had improved event-free survival (EFS) and pathological complete response (pCR) compared with those who received neoadjuvant chemotherapy alone.
The results from the Phase III placebo-controlled AEGEAN clinical trial were presented at the AACR Annual Meeting 2023, held April 14-19.
“Non-small cell lung cancer remains the leading cause of cancer mortality, and historically, about half of patients who undergo resection experience recurrence,” said presenter John V Heymach, Chair of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center. “Anything we can do to increase cure rates for these patients could potentially be a tremendous advance.”
Recent studies indicate the benefit from the use of an adjuvant immune checkpoint inhibitor in NSCLC, especially in patients with PD-1-positive tumours, but whether a more comprehensive approach could improve outcomes has yet to be established.
The AEGEAN clinical trial
In AEGEAN, a randomised, double-blind, placebo-controlled trial, 802 patients with treatment-naïve resectable NSCLC, irrespective of PD-L1 expression, were randomly assigned (1:1) to receive either neoadjuvant durvalumab plus platinum-based chemotherapy or neoadjuvant placebo plus platinum-based chemotherapy every three weeks for four cycles. Following surgery, patients continued to receive either durvalumab or placebo every four weeks for up to 12 cycles.
Following neoadjuvant treatment, pCR was 17.2% in the treatment arm, versus 4.3% in the placebo arm, a difference of 13.0%. Overall, 77.6% of patients in the treatment arm and 76.7% of patients in the placebo arm underwent surgery following neoadjuvant therapy.
After a median follow-up time of 11.7 months, median EFS was not reached in the durvalumab-based regimen arm, versus 25.9 months in the chemotherapy alone arm. Patients in the durvalumab-based regimen arm showed a 32% reduction in the risk of disease progression precluding definitive surgery, disease recurrence, or death compared with those in the chemotherapy alone arm.
“We are excited to see that the trial has achieved both its primary endpoints of improving pCR and significantly reducing the likelihood of disease progression, recurrence, or death,” Heymach said. “The good news for patients with NSCLC is there are now multiple different regimens that have shown improvements in outcomes. This study has laid the foundation that we can build on by designing new combination regimens on top of this effective backbone.”
He added: “This is a new treatment paradigm for this patient population, but one that requires investment from multidisciplinary teams – a greater integration of medical oncology, molecular pathology, and surgical oncology teams all working together to improve clinical outcomes.”