Exploratory Analysis of ADRIATIC Sheds Light on Metastases Outcomes With Durvalumab Consolidation in LS-SCLC

Findings from the phase 3 ADRIATIC study suggest that durvalumab consolidation reduced the rate of extrathoracic metastases in patients with limited-stage small-cell lung cancer (LS-SCLC).

Suresh Senan, MRCP, FRCR, PhD, of the VU University Medical Centre, presented the data during the European Lung Cancer Congress 2025 in Paris, France. The new data from ADRIATIC resulted from exploratory analyses of disease progression patterns among patients receiving durvalumab after concurrent chemoradiotherapy (cCRT) as a treatment for LS-SCLC in the ADRIATIC trial.

Dr. Senan explained that in the first planned interim analysis of ADRIATIC, durvalumab consolidation showed significant improvements in overall survival (OS) and progression-free survival compared to placebo in patients with LS-SCLC who did not have progression after cCRT.

The study included patients with inoperable stage I or II LS-SCLC, as well as stage III LS-SCLC. The study investigators randomized patients to receive durvalumab (n=264), durvalumab plus tremelimumab, or placebo (n=266). The durvalumab plus tremelimumab arm remains blinded, Dr. Senan explained. The researchers stratified patients by disease stage and use of prophylactic cranial irradiation.

Study investigators classified the first site of progression as intrathoracic if there were lesions within the lungs. The first site of progression was classified as extrathoracic if there were lesions outside the lungs, including the chest wall and diaphragm. Patients who only had intrathoracic progression were censored in time to extrathoracic progression or death analysis and vice versa, according to the study investigators. In the analyses evaluating death and time to progression to the brain or central nervous system, patients with extrathoracic progression in other locations only or intrathoracic progression only were censored. The data cut-off date was January 15, 2024.

At the time of the data cut-off, 52.7% of patients receiving durvalumab had progression or death, compared with 63.5% of those receiving placebo. The time to intrathoracic progression or death and the time to extrathoracic progression or death were both “prolonged” with durvalumab compared to placebo. The rate of intrathoracic progression “was similar” between the durvalumab and placebo arms, but the rate of extrathoracic progression was lower with durvalumab.

Extrathoracic lesions at first progression occurred in 19.7% of patients receiving durvalumab, compared with 29.9% of those receiving placebo. Extrathoracic lesions at first progression occurred “mostly in a single organ” in both arms, with the most common site being the brain or central nervous system (Table 1).

Table 1. Progression details for durvalumab versus placebo arms in ADRIATIC.

Brain or central nervous system progression occurred in 6.8% of those receiving durvalumab and 12.4% of those receiving placebo. The rates of first progression with brain or central nervous system metastases were lower with durvalumab than with placebo for patients who received prophylactic cranial irradiation (2.8% with durvalumab versus 6.3% with placebo) and those who did not (11.5% with durvalumab and 19.5% with placebo, Table 2).

Table 2. Time to brain/central nervous system progression or death in durvalumab and placebo arms in ADRIATIC.

Based on these results, Dr. Senan and colleagues concluded that the “findings suggest” that durvalumab consolidation reduced the rate of extrathoracic metastases and prolonged time to progression or death for intrathoracic and extrathoracic metastases, including brain and central metastases, and that durvalumab reduced brain and central nervous system metastases “regardless” of PCI use.

Reference

Senan S, Cheng Y, Spigel D, et al. Patterns of disease progression with durvalumab (D) after concurrent chemoradiotherapy (cCRT) in limited-stage small-cell lung cancer (LS-SCLC): Results from ADRIATIC. Abstract 297MO presented at: European Lung Cancer Congress 2025, March 26-29; Paris, France.