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

Abstract

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.