Concurrent Radiotherapy With Tarlatamab Demonstrates Favorable Safety and Encouraging Local Tumor Control in Extensive-Stage Small Cell Lung Cancer

Clinical Summary:

• Design/Population: This multicenter, real-world retrospective analysis from the DLL3 PanTUMOR database evaluated 109 patients with extensive-stage small cell lung cancer (ES-SCLC) treated with tarlatamab, including 23 who received concurrent radiotherapy, most commonly stereotactic radiotherapy for brain metastases.

• Key Outcomes: Grade 3 or higher radiotherapy-related toxicity occurred in 4.3% of patients, and no delayed cytokine release syndrome (CRS) or immune effector cell–associated neurotoxicity syndrome (ICANS) was observed following completion of the tarlatamab step-up dosing phase. Tumor regression at irradiated sites occurred in 83.3% of patients. Median progression-free survival was 4.6 months with concurrent radiotherapy versus 3.1 months with tarlatamab alone, while median overall survival was not reached versus 7.5 months, although neither difference was statistically significant.

• Clinical Relevance: Concurrent radiotherapy during tarlatamab treatment was associated with a low incidence of severe radiotherapy-related toxicity and encouraging local tumor control, supporting the feasibility of this approach and warranting prospective evaluation to better define its impact on clinical outcomes in ES-SCLC.

Results from a multicenter, real-world retrospective analysis demonstrated that concurrent radiotherapy administered during tarlatamab treatment was associated with a low incidence of severe radiotherapy-related toxicity and encouraging local tumor control in patients with extensive-stage small cell lung cancer (ES-SCLC).

"SCLC is an aggressive malignancy in which radiotherapy remains integral across both limited and extensive stages," stated Diana Kim, PharmD, The University of Kansas Cancer Center, Westwood, Kansas, and coauthors. "Tarlatamab has shown improved survival versus chemotherapy and is the preferred second-line therapy.. [however] early tarlatamab studies restricted radiotherapy use limiting knowledge of concurrent use."

Investigators analyzed data from the DLL3 PanTUMOR database, including 109 adults treated with tarlatamab for ES-SCLC between May 2024 and July 2025. Twenty-three patients received radiotherapy after initiating tarlatamab (concurrent radiotherapy group), while 86 received tarlatamab without radiotherapy. Stereotactic radiotherapy was the most commonly used modality (56.5%) and was primarily delivered for brain metastases. The primary end point was the incidence of grade ≥3 radiotherapy-related adverse events. Secondary end points included overall survival (OS), progression-free survival (PFS), tumor regression at irradiated sites, treatment discontinuation due to adverse events, and maximum CRS or ICANS grade.

Only one patient (4.3%) experienced grade ≥3 radiotherapy-related toxicity following whole-brain radiotherapy. No delayed CRS or ICANS events occurred after completion of the tarlatamab step-up dosing phase.

Tumor regression at irradiated sites was observed in five of six evaluable patients (83.3%). Median OS was not reached in the concurrent radiotherapy group compared with 7.5 months in the tarlatamab-alone group (P = .155). Median PFS was 4.6 months and 3.1 months, respectively (P = .606). Treatment discontinuation because of adverse events did not differ significantly between the groups.

“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," concluded Dr Kim et al. 

Source:

Kim D, Blocker S, Cavalieri CC, et al. Outcomes of Concurrent Radiotherapy With Tarlatamab in Extensive-Stage Small Cell Lung Cancer From the DLL3 PanTUMOR Database. Clin Lung Cancer. Published online January 30, 2026. doi:10.1016/j.cllc.2026.01.007