IMMUNOTHERAPY may offer meaningful benefit for patients with combined small-cell lung cancer, a rare and aggressive tumor subtype that has historically lacked clear treatment strategies. A real-world analysis of 30 patients has provided new insights into clinicopathological features and outcomes, suggesting that immune checkpoint blockade could play a valuable role in disease control.
Combined small-cell lung cancer is defined by the coexistence of small-cell lung cancer with any histological type of non-small cell lung cancer, most often squamous cell carcinoma, adenocarcinoma, or large-cell neuroendocrine carcinoma. In this study, the majority of patients were men, though two-thirds were non-smokers. The most frequent coexisting histologies were squamous cell carcinoma and adenocarcinoma, followed by large-cell neuroendocrine carcinoma.
Patients received a range of systemic therapies including immunochemotherapy, platinum-based chemotherapy, and targeted regimens such as anti-EGFR or anti-VEGF therapy. Notably, most patients receiving immunotherapy were treated with the PD-1 inhibitor serplulimab. Among 27 patients with measurable disease, the response rate was 51.9% and the disease control rate reached 85.2%. Median progression-free survival was 9.7 months overall.
When stratified by histological subtype, patients with large-cell neuroendocrine carcinoma components showed a longer progression-free survival than those with adenocarcinoma or squamous cell carcinoma. Treatment effect also appeared to vary by modality. Immunotherapy achieved longer disease control than chemotherapy or targeted therapy, although the differences were not statistically significant given the small cohort size.
These results suggest that combined small-cell lung cancer is heterogeneous in its clinical behavior and may respond differently depending on histology and treatment approach. Importantly, the findings highlight immunotherapy as a potentially beneficial strategy, supporting the integration of immune checkpoint inhibitors into future treatment algorithms. The authors emphasize the need for larger prospective studies to validate these observations and guide the development of standardized care pathways.
Reference: Liu G et al. Clinicopathological characteristics and treatment patterns of combined small-cell lung cancer: a real-world single-center study with a mini review. Front Immunol. 2025;16:1652803.