Outcomes of Concurrent Radiotherapy With Tarlatamab in Extensive-Stage Small Cell Lung Cancer From the DLL3 PanTUMOR Database.

[BACKGROUND] Small cell lung cancer (SCLC) is an aggressive malignancy in which radiotherapy remains integral across both limited and extensive stages (ES-SCLC). Tarlatamab has shown improved survival versus chemotherapy and is the preferred second-line therapy. Early tarlatamab studies restricted radiotherapy use limiting knowledge of concurrent use. We evaluated the safety and efficacy of real-world concurrent radiotherapy with tarlatamab in ES-SCLC using the DLL3 PanTUMOR database.

[METHODS] We performed a multicenter retrospective analysis of adults treated with tarlatamab for ES-SCLC between May 2024 and July 2025. Patients receiving radiotherapy after tarlatamab initiation were assigned to the concurrent radiation arm; others formed the nonradiotherapy (non-RT) arm. The primary endpoint was the rate of grade ≥ 3 adverse events attributed to radiotherapy. Secondary endpoints included overall survival (OS), progression-free survival (PFS), tumor regression at irradiated sites, discontinuation due to adverse events, and maximum CRS or ICANS grade.

[RESULTS] Among 109 patients (23 concurrent RT, 86 non-RT), baseline characteristics were balanced. Stereotactic radiotherapy was most common (56.5%), predominantly to the brain. Only 1 patient (4.3%) experienced grade ≥ 3 radiotherapy-related toxicity after whole-brain radiotherapy. Median OS was not reached in the concurrent RT arm versus 7.5 months in non-RT (P = .155); median PFS was 4.6 versus 3.1 months (P = .606). Tumor regression occurred in 5 of 6 evaluable patients (83.3%). No delayed CRS or ICANS were observed after the tarlatamab step-up phase.

[CONCLUSIONS] Concurrent radiotherapy with tarlatamab is safe, with low severe toxicity, frequent local tumor response, and a trend toward improved OS, supporting further study in ES-SCLC.