Concurrent Radiotherapy With Tarlatamab Demonstrates Low Toxicity, Promising Disease Control in Extensive-Stage Small Cell Lung Cancer

Key Clinical Summary:

• Design/Population: A multicenter real-world retrospective analysis from the DLL3 PanTUMOR database evaluated 109 patients with extensive-stage small cell lung cancer treated with tarlatamab, including 23 patients who received concurrent radiotherapy (primarily stereotactic radiotherapy to brain metastases).
• Key Outcomes: Grade ≥ 3 radiotherapy-related toxicity occurred in 4.3% of patients, with no delayed CRS or ICANS after the tarlatamab step-up phase. Tumor regression at irradiated sites occurred in 83.3%. Median PFS was 4.6 vs 3.1 months and median OS was not reached vs 7.5 months (concurrent RT vs no RT), with no significant increase in treatment discontinuation due to adverse events.
• Clinical Relevance: Concurrent radiotherapy during tarlatamab therapy demonstrated low rates of grade 3 or higher adverse events and promising local response rates, supporting its feasibility in routine practice and warranting prospective evaluation to clarify potential survival benefits in ES-SCLC.

In a real-world multicenter retrospective analysis of patients with extensive-stage small cell lung cancer (ES-SCLC), concurrent radiotherapy administered during tarlatamab treatment was associated with low rates of severe toxicity (adverse events grade 3 or higher) and encouraging tumor regression.

Previous research has found tarlatamab to be more effective than standard chemotherapy in the second-line setting, however the impact of concurrent use of tarlatamab with radiotherapy remains unknown. Researchers conducted a multicenter, retrospective analysis to determine the safety and efficacy of real-world concurrent radiotherapy and tarlatamab among patients with ES-SCLC using data from the DLL3 PanTUMOR database. 

The primary end point was the rate of grade 3 or higher adverse events related to radiotherapy and secondary end points were overall survival (OS), progression-free survival (PFS), tumor regression at irradiated sites, discontinuation due to adverse events, and maximum cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS) grade. 

Overall, 109 patients were enrolled and treated with tarlatamab between May 2024 and July 2025. Of which, 23 patients received radiotherapy after tarlatamab initiation (concurrent radiotherapy arm) and 86 patients only received tarlatamab therapy (non-radiotherapy arm). The most common radiotherapy modality was stereotactic radiotherapy (56.5%), primarily targeting brain metastases.

At the time of analysis, 4.3% experienced grade ≥3 radiotherapy-related toxicity following whole-brain radiotherapy. No delayed CRS or ICANS events were observed after completion of the tarlatamab step up phase. Tumor regression at irradiated sites occurred in 83.3%. 

The median OS was not reached in the concurrent radiotherapy group compared with 7.5 months in the non-radiotherapy group ( P = .155) and the median PFS was 4.6 months versus 3.1 months, respectively (P = .606). No significant differences between groups were observed in treatment discontinuation due to adverse events.

The researchers concluded, “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.”

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