Adjuvant chemotherapy has been linked to a 5% increase in 5-year survival rates for patients with a completely resected early-stage NSCLC. However, approximately 60% of these patients still experience relapse, creating a need for additional adjuvant treatment options.
PD-(L)1 inhibitors, including durvalumab, have become standard treatment options for resectable NSCLC in the adjuvant, neoadjuvant, and peri-operative settings, according to Glenwood Goss, MD, BCh, FAPSA, FRCPC, Emeritus Professor of Medicine and Senior Clinical Researcher at the Ottawa Hospital Research Institute and the University of Ottawa, Canada.
The phase III BR.31 trial evaluated the efficacy and safety of adjuvant durvalumab compared to placebo in patients with completely resected stage IB–IIIA non-small cell lung cancer (NSCLC). This is the first trial to test the use of durvalumab as adjuvant therapy alone in the early lung cancer setting. In addition, the trial was an academic effort involving different international cooperative groups.
Prof. Goss presented the findings from the BR.31 trial during a proffered paper session at the 2024 European Society for Medical Oncology (ESMO) Congress in September.
Previous adjuvant immunotherapy trials have demonstrated improved disease-free survival (DFS) rates in some populations, however, improvements in overall survival (OS) have been limited. In the BR.31 trial of early-stage NSCLC, adjuvant durvalumab did not demonstrate significant improvement in DFS.
“We know that these agents are effective in improving overall survival in more advanced disease and our task moving forward is to understand the biology and to ask how best to integrate these agents in the earlier setting whilst limiting the toxicity experienced by patients,” Prof. Goss said.
The study included patients with stage IB to IIIA NSCLC who had undergone complete resection and had an ECOG performance status of 0 to 1. The study enrolled patients with EGFR mutations or ALK-positive disease, however, they were not included in the primary DFS analysis. A total of 1,827 patients enrolled in the trial and 1,415 patients were randomized to receive either durvalumab (944) or placebo (471).
All patients received a platinum doublet chemotherapy, followed by surgery, and were then randomized to receive either durvalumab or placebo at a dosage of 20 mg/kg every 4 weeks for 12 months, starting 3 or more weeks post-surgery.
The primary endpoint was DFS in patients with a PD-L1 expression of 25% or higher and EGFR-/ALK-negative disease. Key secondary endpoints included DFS in patients with a PD-L1 expression of 1% or greater and an EGFR or ALK mutation; DFS in all patients with an EDFR- or ALK-negative disease regardless of PD-L1 expression; DFS in all patients with a PD-L1 expression of 25% or more; DFS in all PD-L1 patients with an expression of 1% or more; and DFS in all randomized patients.
Additional secondary endpoints included OS across the six subpopulations, safety, and quality of life.
The median follow-up period was 60 months. In the durvalumab arm, the median DFS for patients with a PD-L1 expression of 25% or more was 70 months, compared to 60 months in the placebo arm. For patients with a PD-L1 expression greater than 1%, the DFS was 60 months in the durvalumab arm, while the placebo arm reported a DFS of 54 months. Patients in the PD-L1 all-comer subpopulation had a median DFS of 60 months in the durvalumab arm and 54 months in the placebo arm.
The safety profile of durvalumab was consistent with the known adverse events (AEs) observed in larger phase III trials. The rate of any AEs for anyone who received at least one dose of treatment was 94% in the durvalumab cohort and 92% in the placebo cohort.
Serious AEs that were possibly related to treatment occurred in 10% of the durvalumab cohort and 4% of the placebo cohort. AEs leading to treatment discontinuation, which were also potentially related to the treatment, were reported in 12% of the durvalumab cohort and 3% of the placebo cohort.
In patients with resectable NSCLC, neoadjuvant chemo-immunotherapy, including durvalumab,and perioperative chemo-immunotherapy has been shown to improve pathological complete response (pCR) and event-free survival (EFS) when compared to neoadjuvant chemotherapyalone.
The study’s outcomes suggest that the presence of the primary disease and associated tumor antigens may be necessary for optimal efficacy, according to Prof. Goss. These valuable insights may help guide future research and potential treatment options for patients with resectable NSCLC, he said.
