Consolidative Thoracic Radiotherapy With Atezolizumab Maintenance in Extensive-Stage Small Cell Lung Cancer: The Phase 2 TREASURE Randomized Clinical Trial (AIO-TRK-0320).

Importance: Chemoimmunotherapy followed by immunotherapy maintenance is the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), yet data regarding efficacy and safety of consolidative thoracic radiotherapy (TRT) are lacking. Objective: To determine whether combining consolidative TRT with immunotherapy maintenance in ES-SCLC is safe and improves patients' overall survival (OS) and progression-free survival (PFS). Design, Settings, and Participants: This was a multicenter open-label phase 2 randomized clinical trial recruiting patients from September 2020 to August 2022 in Germany and Austria, with the last follow-up visit in September 2024. Eligible patients had ES-SCLC with at least stable disease after induction chemoimmunotherapy (carboplatin-etoposide-atezolizumab). Although the database was locked in April 2025, a post hoc survival update was performed in April 2026. Data were analyzed from April 2025 to April 2026. Interventions: Randomized (1:1) to either atezolizumab maintenance combined with consolidative TRT (30 Gy in 10 fractions) (arm A) or atezolizumab maintenance alone (arm B). Main Outcome and Measure: OS (time from randomization to death due to any cause). Results: Of 96 patients assessed for eligibility, 68 patients were randomized; recruitment was prematurely terminated due to safety concerns. Median OS in the combination arm was numerically shorter compared to atezolizumab only (6.7 months [95% CI, 5.1-9.0] vs 13.4 months [95% CI, 10.7-17.5]; HR, 1.55 [95% CI, 0.90-2.69]; P = .34), while median PFS was similar (2.4 months [95% CI, 1.3-3.9] vs 2.6 months [95% CI, 1.2-3.9]; HR, 0.92 [95% CI, 0.54-1.55]; P = .85). TRT plus atezolizumab was accompanied by higher frequency of severe adverse events (SAEs) (19 patients [61.3%] vs 6 patients [18.2%]; P < .001) and fatal outcomes (6 patients [19.4%] vs 1 patient [3.0%]; P = .04). Safety analysis revealed predominance of infection and respiratory disorder-related SAEs, possibly facilitated by a depletion of lymphocytes observed specifically in patients after TRT, and by a lower single breath diffuse capacity of the lungs for carbon monoxide in patients with fatal AEs in arm A. No further risk factors were identified, given that baseline characteristics were well balanced between both arms and between patients with and without SAEs, including fatal SAEs. Conclusions and Relevance: In this randomized clinical trial, TRT combined with immunotherapy increased toxic effects in unselected patients with ES-SCLC without survival benefit, presumably due to radiation-induced lymphocyte depletion facilitating infections. Cautious patient selection and further investigation to identify those who may benefit without undue risk are required. Trial Registration: ClinicalTrials.gov Identifier: NCT04462276.