Real-World Analysis Evaluates Survival and Quality of Life Patterns of Third-Line Systemic Therapies for ES-SCLC

Key Clinical Summary:

• Design/Population: A prospective nationwide German registry analysis (CRISP; NCT02622581) evaluated 82 patients with extensive-stage small cell lung cancer initiating third-line systemic therapy after prior first- and second-line treatment, most of whom had received platinum-based chemotherapy plus immune checkpoint inhibitors and had platinum-resistant disease.
• Key Outcomes: Median real-world PFS was 2.2 months and median real-world OS was 4.4 months. Objective responses were rare, with limited disease control. Longer survival was observed in patients with a longer chemotherapy-free interval and better performance status. Quality of life remained stable but did not meaningfully improve during 3L therapy.
• Clinical Relevance: In the post–chemoimmunotherapy era, third-line treatment in ES-SCLC provides limited survival benefit and no significant quality-of-life improvement, highlighting the urgent need for novel therapeutic strategies in this refractory population.

In a prospective, real-world nationwide German registry analysis, third-line systemic therapy for patients with extensive-stage small cell lung cancer (ES-SCLC) was associated with modest survival outcomes and stability but did not improve quality of life, underscoring the persistent unmet need in this population despite prior chemoimmunotherapy exposure.

For patients with previously treated SCLC, treatment options past the second line are limited and no standard of care has been established. “This study contributes to that evidence by analyzing treatment patterns, outcomes, and quality of life (QoL) among patients with SCLC receiving 3L therapy, based on a large, prospective German-based registry,” wrote Maximilian Rost, MD, Goethe University Frankfurt, University Hospital, Frankfurt, Germany, and co-authors.

This analysis included 82 patients from the CRISP registry (NCT02622581) who initiated third-line therapy after progression on first-and second-line treatment. The median age at third-line initiation was 64.4 years, 58.5% were male, and 39% had ECOG performance status 1. 

The majority (82.9%) of patients had received platinum-based chemotherapy plus immune checkpoint inhibitors in the first-line setting. Platinum-resistant disease, which was defined as chemotherapy-free interval <90 days before second-line initiation, was present in 82.9% of patients. The most common third-line regimens included paclitaxel (22%), topotecan (22%), and cyclophosphamide/doxorubicin/vincristine (17.1%).

At analysis, the median real-world progression-free survival (rwPFS) was 2.2 months (95% confidence interval [CI], 1.8 to 3.0), and median real-world overall survival (rwOS) was 4.4 months (95% CI, 3.4 to 5.2). Subgroup analyses demonstrated longer rwOS among patients with a longer interval between first and second-line therapy (8.3 months for ≥12 months vs 3.4 months for <6 months). Patients with ECOG 0 to 1 had numerically longer rwOS than those with ECOG ≥2 (5.1 vs 4.4 months). No complete responses were observed, while a partial response occurred in 8.5% of patients, stable disease in 15.9%, and progressive disease in 35.4%, as well as undocumented response in 36.5%.

Patient-reported outcomes assessed by the FACT-L questionnaire were available in 75.6% of patients. Quality-of-life scores remained relatively stable over the course of third-line therapy, without clinically meaningful improvement or deterioration.

Dr Rost and co-authors concluded, “Our data demonstrate the only moderate and not sustainable effectiveness of 3L treatment strategies in the ICI-era. It remains an urgent need to introduce new treatment modalities in this hard to treat patient population.”

Source:

Rost M, Fischer R, Reck M, et al. Treatment patterns, outcome and QoL of ES-SCLC patients receiving third-line therapy – Data from the German CRISP Registry (AIO-TRK-0315): A Brief Report. JTO Clinical and Research Reports. Published online January 24, 2026. doi:10.1016/j.jtocrr.2026.100959