Temporal trends in small-cell lung cancer trials registered on ClinicalTrials.gov: a cross-sectional analysis...

Small-cell lung cancer (SCLC) has undergone important therapeutic advances in recent years, including the incorporation of programmed death-ligand 1 (PD-L1) inhibitors into first-line treatment for extensive-stage disease and the emergence of novel therapies for relapsed disease. Whether the characteristics of registered SCLC clinical trials have evolved in parallel with these advances remains incompletely understood. This study aimed to characterize temporal changes in the design, sponsorship, and geographic distribution of interventional SCLC trials registered on ClinicalTrials.gov between 1996 and 2025.

In this cross-sectional study of ClinicalTrials.gov registry records, interventional studies with start dates between January 1, 1996, and December 31, 2025, were identified using the condition terms "Small-Cell Lung Cancer" or "SCLC". Two oncologists independently screened eligible records according to predefined inclusion and exclusion criteria, with disagreements resolved by a third reviewer. Trial characteristics, including phase, enrollment size, masking, allocation, funding source, geographic participation, and recruitment status, were extracted. Categorical variables were summarized descriptively and compared across six 5-year start-year intervals using Pearson χ² or Fisher's exact tests, as appropriate. The Cochran-Armitage trend test was used to evaluate temporal trends in industry sponsorship.

A total of 825 interventional SCLC trials were included, of which 97.7% evaluated therapeutic interventions. Phase 2 studies predominated (55.7%), 48.4% enrolled fewer than 50 participants, and 91.5% were open-label. Among trials reporting allocation, 69.0% were randomized. Trial activity was concentrated in the United States and China and increased markedly after 2016, with 63.3% of all included trials initiated between 2016 and 2025. Although non-industry funding remained the most common overall, the proportion of industry-sponsored trials increased significantly over time, from 10.3% during 1996-2000 to 37.8% during 2021-2025 (trend P<0.0001).

Registered SCLC clinical trial activity has expanded substantially during the past decade, reflecting renewed therapeutic development in this disease. Nevertheless, the trial portfolio remains dominated by early- and mid-phase, open-label studies with relatively small enrollment. These findings highlight the need for larger, internationally collaborative, confirmatory trials and more robust evidence generation to translate emerging therapeutic advances into improved outcomes for patients with SCLC.