Novel Gene Panel Facilitates Biomarker-Guided Chemo-Immunotherapy in Extensive-Stage SCLC

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A novel gene panel offered predictive value for first-line treatment of small cell lung cancer with carboplatin, etoposide, and atezolizumab.

A newly validated, 47-gene panel shows promise as a predictive and prognostic tool for patients with extensive-stage small cell lung cancer (ES-SCLC) receiving first-line chemo-immunotherapy. Researchers presented the findings at the 2025 ASCO Annual Meeting.

Researchers developed the SCLC comprehensive index (SCI) to stratify patients from Seoul National University Hospital into high-, intermediate-, and low-risk groups with significantly different survival outcomes.

Chemo-immunotherapy, specifically carboplatin, etoposide, and atezolizumab, has become the standard of care for first-line treatment of ES-SCLC, supported by the IMpower133 and CASPIAN trials.

“However, there are currently no validated biomarkers to predict treatment response or long-term outcomes in this population,” said Songji Oh and colleagues. “This study aimed to develop a SCI signature using RNA profiling with the nCounter system to predict chemo-immunotherapy outcomes.”

Panel Stratifies Patients by Risk

The researchers developed the panel based on transcriptomic data from IMpower133. Using K-means clustering, the researchers identified genes across key tumor biology domains, including neural (n=7), epithelial-to-mesenchymal transition (n=5), tumor-associated macrophages (n=5), and T-cell inflamed signature (TIS) genes (n=18), as well as genes for SCLC subtyping, potential therapeutic targets, and housekeeping functions.

In the validation cohort of 93 patients, the median age was 69 years, and most were male (M:F ratio, 7.5:1). SCLC molecular subtypes included ASCL1 (39%), NEUROD1 (24%), POU2F3 (3%), YAP1 (32%), and TIS-inflamed (9%).

The panel stratified patients into the following groups:

• High-risk (n=29);
• Intermediate-risk (n=48); and
• Low-risk (n=16).

Survival Outcomes Differ by Subgroup

Across all patients, the median progression-free survival (PFS) and overall survival (OS) were 5.7 months and 12.9 months, respectively.

In the subgroups, the median PFS was 4.8 months for high-risk patients, 5.9 months for intermediate-risk patients, and 9.9 months for low-risk patients. The median OS for each respective group was 8.1, 14.3, and 24.4 months.

Statistical analysis showed a five-fold increased risk of death in high-risk versus low-risk patients (HR, 5.03; P<0.001), with similarly significant differences in PFS (HR, 4.68; P<0.001). The SCI model’s predictive power was confirmed in the IMpower133 cohort, where high-risk patients also had significantly worse PFS (HR, 2.33; P=0.001) and OS (HR, 3.47; P<0.001).

“The SCI 47-gene panel based on IMpower133 transcriptome was validated through nCounter analysis system and effectively stratified ES-SCLC patients into distinct risk groups with strong predictive and prognostic capacities,” the researchers concluded. “It provides a practical biomarker for guiding immunotherapy in patients with ES-SCLC.”