Results from the phase 3 BR.31 trial indicate that adjuvant durvalumab (Imfinzi) following complete resection, with or without chemotherapy, did not significantly improve disease-free survival (DFS) compared to placebo in patients with EGFR- or ALK-negative non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression levels. The findings were presented at the 2024 European Society of Medical Oncology (ESMO) Congress.
In patients with PD-L1 expression of 25% or more, the median DFS in the durvalumab arm was 69.9 months (95% CI, 57.6-NR) compared to 60.2 months (95% CI, 47.7-NR) in the placebo arm (HR, 0.935; 95% CI, 0.706-1.247; P = .642). The 18-month DFS rate in the durvalumab arm was 75.1% (95% CI, 69.9%-79.6%) versus 70.5% (95% CI, 62.5%-77.1%) in the placebo arm. The 24-month rate was 71.2% (95% CI, 65.7%-75.9%) versus 68.5% (95% CI, 60.4%-75.3%), and the 36-month rate was 63.9% (95% CI, 58.2%-69.0%) versus 62.4% (95% CI, 54.1%-69.6%).
Similarly, for patients with PD-L1 expression of 1% or more, the median DFS was 59.9 months (95% CI, 48.4-77.9) in the durvalumab arm and 60.3 months (95% CI, 43.8-80.9) in the placebo arm (HR, 0.989; 95% CI, 0.788-1.248; P = .926). The 18-month DFS rates were 73.4% (95% CI, 69.0%-77.2%) versus 70.1% (95% CI, 63.6%-75.7%); 24-month rates were 68.6% (95% CI, 64.1%-72.7%) versus 67.0% (95% CI, 60.4%-72.7%); and 36-month rates were 60.2% (95% CI, 55.4%-64.5%) versus 60.1% (95% CI, 53.4%-66.3%), in the durvalumab and placebo arms, respectively.
Study Design and Patient Population
The BR.31 trial enrolled patients with stage IB to IIIA NSCLC who had undergone complete resection, had an ECOG performance status of 0 to 1, and EGFR-mutated/ALK-positive disease. Participants received a platinum doublet followed by surgery and randomization at 3 weeks or more. They were then randomly assigned 2:1 to receive either durvalumab at 20 mg/kg every 4 weeks for 12 months or a matched placebo.
The primary endpoint was investigator-assessed DFS in patients with PD-L1 expression of 25% or more and EGFR- or ALK-negative disease. Secondary endpoints included DFS in patients who had PD-L1 expression of 1% or more and EGFR- or ALK-negative disease, all patients with PD-L1 expression of 25% or more, all randomly assigned patients, PD-L1 all comers with EGFR- or ALK-negative disease, and all patients with PD-L1 expression of 1% or more; overall survival; adverse effects (AEs); and quality of life.
Key Findings and Implications
According to Glenwood Goss, MB, BCh, FCPSA, FRCPC, a professor of medicine at the University of Ottawa, the outcomes suggest that the presence of primary disease and associated tumor antigens, as in the perioperative approach, may be required for optimal efficacy in NSCLC.
Safety Profile
The safety analysis, which included all patients who received at least one dose of treatment, showed that any AEs occurred in 93.8% of patients in the durvalumab arm and 92.3% in the placebo arm. Grade 3/4 AEs occurred in 23.5% versus 19.6%, and AEs leading to death occurred in 0.7% versus 0.2% between the durvalumab and placebo arms, respectively. Serious AEs were observed in 18.8% versus 15.4%, and AEs leading to discontinuation occurred in 14.0% versus 5.1% in the durvalumab and placebo arms, respectively.
