Real-World CRISP Analysis Highlights Limited Benefit of Third-Line Therapy in Extensive-Stage Small Cell Lung Cancer

Clinical Summary:

• Design/Population: This prospective nationwide analysis of the German CRISP registry evaluated patients with extensive-stage small cell lung cancer (ES-SCLC) who initiated third-line systemic therapy after prior first- and second-line treatment, most of whom had received platinum-based chemoimmunotherapy and had platinum-resistant disease.

• Key Outcomes: Median real-world progression-free survival was 2.2 months and median real-world overall survival was 4.4 months. Objective responses were uncommon, and quality of life remained generally stable throughout third-line treatment without clinically meaningful improvement. Longer survival was observed among patients with longer chemotherapy-free intervals and better performance status.

• Clinical Relevance: These findings highlight the limited effectiveness of currently available third-line therapies for ES-SCLC in the chemoimmunotherapy era and underscore the need for more effective treatment strategies for this heavily pretreated population.

Results from a prospective, nationwide analysis of the German CRISP registry demonstrated that currently available third-line systemic therapies provide limited clinical benefit for patients with extensive-stage small cell lung cancer (ES-SCLC) following first-line chemoimmunotherapy.

"Recurrent ES-SCLC remains a major therapeutic challenge," stated Maximilian Rost, MD, Goethe University Frankfurt, University Hospital, Frankfurt, Germany, and coauthors. "Although immune checkpoint inhibitors, bispecific antibodies, and antibody-drug conjugates offer promise in early lines, outcomes beyond the second line (2L) remain poor." 

This prospective analysis included 82 patients from the multicenter CRISP registry who initiated third-line systemic therapy after disease progression following first- and second-line treatment. The median age at third-line treatment initiation was 64.4 years, 58.5% of patients were male, and most had brain, liver, or bone metastases. More than 80% had previously received platinum-based chemotherapy plus an immune checkpoint inhibitor, and 82.9% had platinum-refractory disease. The most commonly administered third-line regimens were paclitaxel (22%), topotecan (22%), and cyclophosphamide, doxorubicin, and vincristine (17.1%).

Median real-world progression-free survival was 2.2 months, and median real-world overall survival was 4.4 months. No complete responses were observed. Partial responses occurred in 8.5% of patients, stable disease in 15.9%, and progressive disease in 35.4%, although response assessments were unavailable for 36.5% of patients.

Exploratory analyses demonstrated numerically longer overall survival among patients with longer intervals between first- and second-line therapy, increasing from 3.4 months for patients with an interval of less than 6 months to 8.3 months for those with an interval of at least 12 months. Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1 also experienced numerically longer survival than those with poorer performance status.

Patient-reported outcomes were available for 63 patients (75.6%). Functional Assessment of Cancer Therapy–Lung (FACT-L) scores remained generally stable throughout third-line treatment, indicating maintenance of quality of life without clinically meaningful improvement.

"Outcomes in [third-line] therapy in ES-SCLC remain poor among subgroups, even in predominantly ICI-pretreated patients, strongly highlighting the need for better [third-line] strategies," concluded Dr Rost et al. "These real-world data are critical to support shared decision-making, helping clinicians and patients weigh the limited benefits of further chemotherapy against best supportive care."

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 Clin Res Rep. Published online: January 24, 2026. doi: 10.1016/j.jtocrr.2026.100959