ADRIATIC

At ASCO 2025, Prof Dr Christophe Dooms, a respiratory oncologist from the University Hospital Leuven in Belgium, interviewed Prof Dr David Barbie, a medical oncologist at the Dana-Farber Cancer Institute, Boston, about the post-hoc exploratory clinical and biomarker analysis of the ADRIATIC trial. Prof Barbie explained that the ADRIATIC trial aimed to test the effectiveness of durvalumab as a consolidation treatment after chemoradiotherapy in patients with limited-stage SCLC. The trial had previously shown that adding durvalumab significantly improved OS, becoming the new standard of care for these patients. The current analysis focused on early progressors compared to those with long-term PFS.

The analysis revealed that many early progressions occurred within the first six months, while long-term survivors demonstrated a plateau in progression-free survival (PFS). Interestingly, clinical characteristics such as earlier-stage disease, use of prophylactic cranial irradiation, and hyperfractionated radiotherapy were more common in long-term progressors. The biomarker analysis included CD8 T cell density and MHC class 1 expression, which were higher in long-term progressors, regardless of whether patients received durvalumab or placebo. However, the most notable finding was in the cGAS-STING pathway and T-cell inflamed markers, where higher expression was observed in the durvalumab arm, suggesting that these biomarkers could potentially predict better responses to immunotherapy.

Prof Barbie emphasised that while the data showed promising trends, it’s too early to consider altering treatment based on biomarkers. Future research will likely explore spatial patterns of immune cell infiltration and ways to “inflame” tumours that lack sufficient immune response. He also mentioned that EZH2 inhibitors could potentially help revert cold tumours into more inflamed states, thereby improving their response to chemoradiotherapy and immunotherapy.

Prof Barbie concluded that while chemoradiotherapy alone is important, the future may see more strategies aimed at enhancing the tumour’s immune environment to further improve outcomes.