Treatment Patterns, Outcome, and Quality of Life of Patients With Extensive-Stage SCLC Receiving Third-Line Therapy-Data From the German CRISP Registry (AIO-TRK-0315): A Brief Report.

Introduction: Recurrent extensive-stage SCLC (ES-SCLC) remains a major therapeutic challenge. Although immune checkpoint inhibitors (2Ls), bispecific antibodies, and antibody-drug conjugates offer promise in early lines, outcomes beyond the second line (2L) remain poor. Real-world data on third line (3L) treatment patterns, clinical outcomes, and quality of life (QoL) after ICI-based first line (1L) therapy are limited but critical to inform clinical decision-making. Methods: CRISP is a prospective, multicenter registry for patients with lung cancer in Germany. In-depth patient and tumor characteristics, details about treatments, outcome, and patient-reported outcomes data are collected. Between September 2019 and April 2021, 114 sites in Germany recruited 518 patients with ES-SCLC, of which 82 started 3L therapy. Results: Of 82 patients, 58.5% were male and 79.3% were below 70 years old. At 3L start, Eastern Cooperative Oncology Group performance score was 0 in 18.3%, 1 in 39.0%, and more than or equal to 2 in 19.5% (23.2% unknown). In the 1L setting, 68 patients (82.9%) received platinum-based chemotherapy plus ICI and 68 (82.9%) were platinum refractory (time to next treatment < 3 mo). Furthermore, 2L therapy consisted of topotecan (47.6%) and other chemotherapies (52.4%). The three most common 3L regimens were paclitaxel (22%), topotecan (22%), and cyclophosphamide, doxorubicin, vincristine (17.1%). Local radiotherapy was used in 19 patients (23.2%) in the 3L. Median real-world progression-free survival was 2.2 months (95% confidence interval: [1.8-3.0]), and real-world overall survival was 4.4 months (95% confidence interval: [3.4-5.2]). Exploratory analyses revealed numerically longer real-world overall survival with increasing time between 1L and 2L initiation (<6 mo: 3.4 mo; 6-11 mo: 4.4 mo; ≥ 12 mo: 8.3 mo) and in patients with Eastern Cooperative Oncology Group performance score 0 to 1 versus more than or equal to 2 (5.1 versus 4.4 mo). QoL, assessed by FACT-L subscales, remained stable during follow-up. Conclusions: Outcomes in 3L therapy in ES-SCLC remain poor among subgroups, even in predominantly ICI-pretreated patients, strongly highlighting the need for better 3L strategies. Although QoL can be preserved, therapeutic efficacy is lacking. 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.