Immune Biomarkers Differentiate Early Progression from Long-Term Survival in Limited-Stage Small-Cell Lung Cancer

Photo Credit: ArtemisDiana

The phase 3 ADRIATIC trial has established the survival benefit of consolidation immunotherapy following concurrent chemoradiotherapy (cCRT) in patients with limited-stage small-cell lung cancer (LS-SCLC), according to findings from ASCO 2025.

A recent exploratory analysis of this trial further investigated the clinical and molecular characteristics of two patient subgroups: early progressors (EPs), defined as those with progression-free survival (PFS) under six months, and long-term progression-free survivors (LTPs), with PFS or censoring beyond 12 months.

Among 264 patients treated with immunotherapy and 266 on placebo, roughly one-third in each arm were EPs, while over one-third achieved LTP status. Clinical characteristics such as sex, performance status, and smoking history were similar across both groups and arms. Notably, progression patterns were comparable between EPs in the immunotherapy and placebo arms, with both experiencing a mix of intrathoracic and extrathoracic disease recurrence. In contrast, progression among LTPs was predominantly intrathoracic and occurred less frequently.

Molecular profiling revealed key differences between EPs and LTPs, particularly within the immunotherapy-treated cohort. LTPs had higher tumor expression of markers associated with a favorable immune microenvironment, including CD8 density, MHC class I, CD8A expression, and T-cell inflamed signatures (TIS). These biomarkers suggest a pre-existing tumor environment more capable of supporting a robust immune response. Trends toward elevated STING pathway activity, associated with enhanced antigen presentation and innate immunity, were also more apparent in LTPs receiving immunotherapy, suggesting its potential role in long-term disease control.

PD-L1 expression rates, however, did not differ significantly between EPs and LTPs, indicating its limited utility as a standalone predictor of response. These findings collectively underscore the importance of a multifaceted immunogenic tumor profile—rather than PD-L1 alone—in identifying patients most likely to benefit from immunotherapy.

“Compared with EPs, LTPs were generally characterized by a pre-cCRT tumor microenvironment more conducive to fostering an [immunotherapy] response, with higher antigen presentation and cytotoxic marker expression potentially enhancing [durvalumab]’s mechanism of action,” the authors of the study concluded.