Dr Heymach on Perioperative Durvalumab in Resectable N2 NSCLC

John Heymach, MD, PhD, professor, chair, David Bruton, Jr Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses findings from an exploratory subgroup analysis of the phase 3 AEGEAN trial (NCT03800134), which evaluated perioperative durvalumab (Imfinzi) plus neoadjuvant chemotherapy in patients with resectable non–small cell lung cancer (NSCLC) and baseline N2 lymph node involvement.

The AEGEAN trial enrolled treatment-naive patients with resectable NSCLC. Patients were randomly assigned to 4 four cycles of platinum-based chemotherapy with either durvalumab at 1500 mg or placebo once every three weeks before surgery, followed by durvalumab or placebo every 4 weeks for 12 cycles after surgery.

The modified intent-to-treat (ITT) population excluded patients with known EGFR or ALK alterations. In the subgroup analysis, efficacy was assessed in a subpopulation with baseline N2 nodal status.

Heymach emphasizes that patients with more advanced lymph node involvement, specifically N2, benefited significantly from the addition of perioperative durvalumab to neoadjuvant chemotherapy. An event-free survival (EFS) benefit was seen across patients with single-station disease (HR, 0.61; 95% CI, 0.39-0.94) and multi-station N2 involvement (HR, 0.69; 95% CI, 0.33-1.38), as well as the overall N2 population (HR, 0.63; 95% CI, 0.43-.80) Importantly, the EFS benefits observed in patients with N2 disease mirrored the findings from the modified ITT population (HR, 0.68; 95% CI, 0.53-0.88).

Additionally, in the overall N2 population, pathological complete response (pCR) rates were higher in the durvalumab arm (16.6%) vs the placebo arm (4.9%; difference, 11.7%; 95% CI, 5.6%-18.4%), as were major pathological response (MPR) rates (32.6% vs. 15.1%; difference, 17.5%; 95% CI: 8.8%-26.0%).

Heymach notes that despite the advanced disease, patients with baseline N2 disease could complete surgery safely, with the rates of lobectomy being comparable with the overall population. The proportion of patients with N2 disease achieving complete resection (R0 resection) was 94.7% in the durvalumab group vs 91.7% in the placebo arm.

In the safety analysis subset for those with N2 disease, the incidence of grade 3/4 adverse effects was comparable between the arms (38.5% for durvalumab vs 41.8% for placebo).