Consolidative Thoracic Radiotherapy Increases Toxicity Without Survival Benefit in Extensive-Stage Small Cell Lung Cancer

Clinical Summary: 

• Design/Population: This multicenter, open-label, phase 2 randomized trial evaluated consolidative thoracic radiotherapy plus atezolizumab maintenance versus atezolizumab maintenance alone in patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease was at least stable following first-line carboplatin, etoposide, and atezolizumab.
• Key Outcomes: The addition of consolidative thoracic radiotherapy did not improve overall survival or progression-free survival and was associated with significantly higher rates of severe adverse events, including infections, respiratory complications, and treatment-related deaths. Recruitment was halted early because of safety concerns.
• Clinical Relevance: These findings do not support the routine addition of consolidative thoracic radiotherapy to atezolizumab maintenance in unselected patients with ES-SCLC and suggest that radiation-induced lymphocyte depletion may contribute to excess toxicity, warranting further investigation in carefully selected populations.

Results from the phase 2 TREASURE trial demonstrated that adding consolidative thoracic radiotherapy  to atezolizumab maintenance increased toxicity without improving survival in patients with extensive-stage small cell lung cancer (ES-SCLC), arguing against routine use of the combination in unselected patients.

According to Fatastuk Bozorgmehr, MD, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany, and coauthors, “chemoimmunotherapy followed by immunotherapy maintenance is the standard first-line treatment for ES-SCLC, yet data regarding efficacy and safety of consolidative thoracic radiotherapy are lacking.” 

In this multicenter, open-label trial, 68 patients with ES-SCLC whose disease was at least stable following induction therapy with carboplatin, etoposide, and atezolizumab were randomized 1:1 to receive atezolizumab maintenance plus consolidative thoracic radiotherapy (30 Gy in 10 fractions) or atezolizumab maintenance alone. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS) and safety. Enrollment was terminated early because of safety concerns.

At analysis, median OS was 6.7 months in the thoracic radiotherapy plus atezolizumab arm compared with 13.4 months in the atezolizumab-alone arm (hazard ratio [HR], 1.55; 95% CI, 0.90 to 2.69; P = .34). Median PFS was 2.4 months and 2.6 months, respectively (HR, 0.92; 95% CI, 0.54 to 1.55; P = .85).

Treatment with consolidative thoracic radiotherapy was associated with significantly greater toxicity. Severe adverse events occurred in 61.3% of patients receiving thoracic radiotherapy plus atezolizumab compared with 18.2% of those receiving atezolizumab alone (P < .001). Fatal adverse events occurred in 19.4% and 3% of patients, respectively (P = .04).  

Safety analyses demonstrated that severe adverse events were predominantly infection- and respiratory disorder-related. Investigators observed persistent lymphocyte depletion following thoracic radiotherapy, suggesting radiation-induced immunosuppression may have contributed to the increased risk of infection. Patients who experienced fatal adverse events in the thoracic radiotherapy arm also had lower baseline single-breath diffusing capacity of the lungs for carbon monoxide, although no additional baseline risk factors were identified.

“In unselected patients with ES-SCLC, consolidative [thoracic radiotherapy] combined with immunotherapy maintenance increased toxic effects without efficacy benefit, arguing against routine use other than in carefully selected patients,”concluded Dr Bozorgmehr et al. “Further investigation of radiation-induced lymphocyte depletion as a potential risk factor is warranted.”

Source: 

Bozorgmehr F, Chung I, Behnisch R, et al. Consolidative thoracic radiotherapy with atezolizumab maintenance in extensive-stage small cell lung cancer. JAMA Oncol. Published online: July 9, 2026. doi: 10.1001/jamaoncol.2026.2330