Adding consolidative thoracic radiotherapy (TRT) to atezolizumab (Tecentriq) maintenance increased severe and fatal toxicity without improving survival in patients with extensive-stage small cell lung cancer (ES-SCLC), according to findings from the phase 2 TREASURE trial (NCT04462276) published in JAMA Oncology.¹ Recruitment was prematurely terminated because of safety concerns.
What did the TREASURE trial show?
Among the 68 patients who were randomly assigned, the median overall survival (OS) in the combination arm was numerically shorter than with atezolizumab alone, at 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). The estimated OS rates in each arm were 30.3% (95% CI, 15.9%-46.1%) vs 56.6% (95% CI, 37.9%-71.6%) at 1 year and 24.2% (95% CI, 11.4%-39.6%) vs 15.7% (95% CI, 5.7%-30.2%).
The median progression-free survival (PFS) was similar between the arms, at 2.4 months (95% CI, 1.3-3.9) with TRT plus atezolizumab vs 2.6 months (95% CI, 1.2-3.9) with atezolizumab alone (HR, 0.92; 95% CI, 0.54-1.55; P = .85). The addition of consolidative TRT did not confer a survival benefit in this unselected population.
What were the safety findings?
TRT plus atezolizumab was associated with a higher frequency of severe adverse effects (SAEs) than atezolizumab alone, occurring in 19 patients (61.3%) vs 6 patients (18.2%; P <.001), and with more fatal AEs, in 6 patients (19.4%) vs 1 patient (3.0%; P = .04). The safety analysis showed a predominance of infection- and respiratory disorder–related SAEs, which the investigators noted may have been facilitated by a depletion of lymphocytes observed specifically in patients after TRT and by a lower single-breath diffusing capacity of the lungs for carbon monoxide among patients with fatal AEs in the combination arm.
Baseline characteristics were well balanced between the arms and between patients with and without SAEs, and no further risk factors were identified.
“In this randomized clinical trial, combining consolidative TRT with atezolizumab maintenance resulted in an unexpected increase of toxic effects, including partially fatal infections and pulmonary disorders, associated with a reduced baseline diffuse capacity of the lungs for carbon monoxide single breath [DLCO SB] and protracted radiation-induced lymphopenia,” lead study author Farastuk Bozorgmehr, MD, of the Department of Thoracic Oncology, Thoraxklinik, Heidelberg University Hospital and National Center for Tumor Diseases (NCT), NCT Heidelberg, and Heidelberg University Hospital, wrote with coauthors in the publication.1 “Thus, in the maintenance setting after chemoimmunotherapy, addition of consolidative TRT cannot currently be recommended outside of clinical trials for unselected patients, and future studies exploring this strategy should consider mitigation strategies, such as dose exposure to highly perfused organs at risk (i.e., lungs, heart, and large vessels), radiotherapy timing relative to immunotherapy cycles, and prospectively defined safety stopping rules.”
What was the TREASURE trial design?
TREASURE (AIO-TRK-0320) was a multicenter, open-label, phase 2 randomized clinical trial that recruited patients in Germany and Austria from September 2020 to August 2022, with the last follow-up in September 2024 and a post hoc survival update in April 2026.2 Eligible patients had ES-SCLC with at least stable disease after induction chemoimmunotherapy with carboplatin, etoposide, and atezolizumab.
Of 96 patients assessed for eligibility, 68 were randomly assigned 1:1 to atezolizumab maintenance combined with consolidative TRT at 30 Gy in 10 fractions or to atezolizumab maintenance alone. The primary outcome was OS. Secondary end points included PFS and the frequency and severity of AEs and serious AEs.
References
- Bozorgmehr F, Chung I, Behnisch R, et al. Consolidative thoracic radiotherapy with atezolizumab maintenance in extensive-stage small cell lung cancer: the phase 2 TREASURE randomized clinical trial (AIO-TRK-0320). JAMA Oncol. Published online July 9, 2026. doi:10.1001/jamaoncol.2026.2330
- Thoracic radiothErapy with atezolizumab in small cell lUng canceR extensive disease (TREASURE). ClinicalTrials.gov. Updated January 30, 2025. Accessed July 24, 2026. https://clinicaltrials.gov/study/NCT04462276
