Thoracic Radiotherapy Added to Atezolizumab Raised Toxicity in SCLC

Adding consolidative thoracic radiotherapy to atezolizumab (Tecentriq) maintenance therapy did not improve survival and was associated with significantly more frequent, and sometimes fatal, adverse events (AEs) compared with atezolizumab maintenance alone in patients with extensive-stage small cell lung cancer (ES-SCLC), according to results from the phase 2 TREASURE trial (NCT04462276) published in JAMA Oncology. The trial was stopped early because of safety concerns.¹

The multicenter, open-label trial enrolled patients across 20 sites in Germany and Austria who had 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 thoracic radiotherapy (30 Gy in 10 fractions; arm A) or atezolizumab maintenance alone (arm B). The primary end point was overall survival.

The trial had been designed to enroll 104 patients to detect a 20% absolute improvement in 12-month survival, but recruitment was paused after 68 patients (34 per arm) had been randomized, and statistical power was substantially reduced as a result. The authors noted that interpretation of the findings should therefore be considered descriptive rather than definitive.

Survival Outcomes

Median overall survival (OS) was 6.7 months (95% CI, 5.1-9.0) in the combination arm vs 13.4 months (95% CI, 10.7-17.5) in the atezolizumab-alone arm (HR, 1.55; 95% CI, 0.90-2.69; P =.34), a difference that did not reach statistical significance given the reduced sample size. Estimated 1-year OS l rates were 30.3% with combination therapy vs 56.6% with atezolizumab alone. Median progression-free survival was similar between arms (2.4 months vs 2.6 months; HR, 0.92; 95% CI, 0.54-1.55; P =.85), a pattern the authors said argues against radiotherapy providing meaningful additional tumor control and instead points to treatment-related toxicity as the likely driver of the survival difference.

Safety and Toxicity

Serious AEs occurred in 19 of 31 patients (61.3%) in the combination arm compared with 6 of 33 patients (18.2%) in the atezolizumab-alone arm (P <.001), and fatal AEs occurred in 6 patients (19.4%) vs 1 patient (3.0%; P =.04). Infections and respiratory disorders, including pneumonitis, were the most common serious AEs in the combination arm. The investigators found that patients who received radiotherapy experienced pronounced and persistent depletion of lymphocytes—a change not seen in leukocyte or neutrophil counts—that coincided with the higher rate of AEs. A lower baseline diffusing capacity of the lungs for carbon monoxide was also associated with fatal AEs among patients who received radiotherapy, though the authors cautioned that this finding should be interpreted cautiously given the small sample size.

The authors noted that these findings are consistent with results from the randomized PACIFIC-2 (NCT03519971) and CheckMate 73L (NCT04026412) trials in non–small cell lung cancer, both of which also found more fatal infections and toxic effects when concurrent thoracic chemoradiotherapy was combined with immunotherapy.^2,3

The authors concluded that consolidative thoracic radiotherapy added to atezolizumab maintenance increased toxic effects without an efficacy benefit in unselected patients with ES-SCLC, likely related to radiation-induced lymphocyte depletion facilitating infection. They stated that this approach cannot currently be recommended outside of clinical trials for unselected patients, and that future studies of this strategy should consider limiting radiation dose exposure to highly perfused organs at risk, adjusting the timing of radiotherapy relative to immunotherapy cycles, and incorporating prospectively defined safety stopping rules. Ongoing biomarker analyses may help identify patient subgroups who could benefit from this approach without excess risk.

REFERENCES

1. 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. 2026 Jul 9:e262330. doi: 10.1001/jamaoncol.2026.2330. Epub ahead of print. PMID: 42424047; PMCID: PMC13352179.

2. Bradley JD, Sugawara S, Lee KH, et al. Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer: The Phase III PACIFIC-2 Study. J Clin Oncol. 2025 Nov 20;43(33):3610-3621. doi: 10.1200/JCO-25-00036. Epub 2025 Oct 13. Erratum in: J Clin Oncol. 2026 Feb 10;44(5):429. doi: 10.1200/JCO-25-03012. PMID: 41082707; PMCID: PMC12622289.

3. De Ruysscher D, Ramalingam S, Urbanic J, et al. CheckMate 73L: A Phase 3 Study Comparing Nivolumab Plus Concurrent Chemoradiotherapy Followed by Nivolumab With or Without Ipilimumab Versus Concurrent Chemoradiotherapy Followed by Durvalumab for Previously Untreated, Locally Advanced Stage III Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2022 May;23(3):e264-e268. doi: 10.1016/j.cllc.2021.07.005. Epub 2021 Jul 19. PMID: 34489161.