Real-World Treatment Pathways in Extensive-Stage SCLC Show Significant Gaps in Care
Key Clinical Summary
- A US real-world analysis of 2573 patients with extensive-stage small cell lung cancer (ES-SCLC) found fragmented treatment patterns beyond first-line (1L) therapy.
- Median overall survival after third-line (3L) therapy was only 4.5 months, with response rates of 11.7%.
- Findings underscore the lack of a clear standard of care and urgent need for novel therapies.
A retrospective analysis of a nationwide US electronic health record (EHR)-derived database revealed poor outcomes and significant treatment variability among patients with extensive-stage small cell lung cancer (ES-SCLC) following first-line platinum-based chemotherapy (PBC). The study, conducted using Flatiron Health data, emphasizes the persistent unmet need for effective therapies in later treatment lines.
Study Findings
Researchers identified 2573 adults with ES-SCLC who received 1L PBC between January 2018 and June 2023. Of these, 992 (38.6%) progressed to second-line therapy, 344 (13.4%) to third-line, and only 114 (4.4%) to fourth-line therapy—highlighting steep attrition between treatment stages.
Treatment beyond 1L was heterogeneous. In second-line therapy, the most common regimens included lurbinectedin (26.5%) and platinum rechallenge (29.3%). In 3L, lurbinectedin-containing and topoisomerase inhibitor regimens were most frequent (21.8% each). No dominant regimen emerged, reflecting the absence of a standard of care.
Clinical outcomes in the 3L cohort were poor. Median real-world overall survival (rwOS) from 3L initiation was 4.53 months (95% CI, 3.71–5.39), while median real-world time to treatment discontinuation or death (rwTTD/D) was 2.56 months. Median time to next treatment or death (rwTTNT/D) was 2.92 months, and the confirmed real-world response rate (rwRR) among 77 evaluable patients was 11.7%.
Subgroup analyses showed only modest differences. Patients with ECOG performance status 0–1 had a slightly longer median rwOS (5.85 months), while those who underwent platinum rechallenge achieved 6.8 months. However, outcomes remained dismal across all groups, underscoring the limited efficacy of current options.
Clinical Implications
These findings paint a sobering picture of real-world ES-SCLC management in the US. While immune checkpoint inhibitors have improved outcomes in first-line settings, disease recurrence is nearly universal, and therapeutic options beyond 1L remain inadequate. The fragmented use of therapies such as lurbinectedin, topotecan, and PD-(L)1 inhibitors—without a clear efficacy leader—reflects both the scarcity of proven regimens and clinician uncertainty in later-line decision-making.
With a median survival under five months after 3L initiation, patients with relapsed or refractory ES-SCLC face a critical lack of durable treatment options. These real-world data reinforce the pressing need for novel, more effective agents—particularly those with manageable toxicity profiles and activity in patients with central nervous system involvement.
Conclusion
This large, multi-institutional US analysis confirms that survival outcomes for patients with ES-SCLC remain poor beyond first-line therapy. With no established standard of care after platinum-based chemotherapy, the findings highlight an urgent call for research and development of novel, effective treatment options in this challenging disease.
Reference
Sankar K, Unni S, Eberl M, et al. Real-world treatment patterns and clinical outcomes in patients with extensive-stage small cell lung cancer treated with first-line platinum-based chemotherapy and ≥ 2 subsequent lines of therapy in the United States. Adv Ther. Published online November 12, 2025. doi:10.1007/s12325-025-03408-z
