Presented during the Lung Cancer—Non–Small Cell Local-Regional/Small Cell/Other Thoracic Cancers Oral Abstract Session at the 2026 ASCO Annual Meeting, Bjorn Henning Gronberg, MD, PhD, reported phase III data evaluating concurrent thoracic radiotherapy with platinum/etoposide chemotherapy and durvalumab in patients with extensive-stage small cell lung cancer.
Extensive-stage small cell lung cancer remains an aggressive thoracic malignancy with poor long-term outcomes despite initial sensitivity to chemotherapy. Chemoimmunotherapy with platinum/etoposide and PD-L1 inhibition has become an important standard approach, but disease progression remains common, and strategies to improve survival continue to be explored.
Thoracic radiotherapy has previously shown benefit in selected patients with extensive-stage SCLC after chemotherapy, and the possibility of synergy between radiotherapy and immunotherapy has created interest in combining thoracic radiotherapy with chemoimmunotherapy. Retrospective data have also suggested that thoracic radiotherapy may improve survival in patients receiving chemoimmunotherapy.
This phase III trial tested whether adding thoracic radiotherapy to carboplatin, etoposide, and durvalumab could improve overall survival in patients with extensive-stage SCLC.
A Phase III Trial Testing Radiotherapy in the Chemoimmunotherapy Era
Eligible patients were adults aged 18 years or older with ECOG performance status 0–1 and stage III–IV disease according to TNM 8 criteria. Patients were ineligible for curative chemoradiotherapy.
Participants were randomized in a 1:1 ratio to receive either chemoimmunotherapy plus thoracic radiotherapy or chemoimmunotherapy alone. Randomization was stratified by the presence of liver metastases and brain metastases.
All patients received 4 courses of carboplatin, etoposide, and durvalumab. Carboplatin was given at AUC 5, etoposide at 100 mg/m² intravenously on days 1–3 or 100 mg/m² intravenously on day 1 followed by 200 mg/m² orally on days 2–4, and durvalumab at 1500 mg every 3 weeks. After the initial treatment phase, durvalumab was continued at 1500 mg every 4 weeks until disease progression, unacceptable toxicity, or patient decision to discontinue.
In the thoracic radiotherapy group, radiotherapy was delivered as 30 Gy in 10 fractions to thoracic lesions. Treatment began 21–28 days after day 1 of the first chemoimmunotherapy cycle.
Prophylactic cranial irradiation at 25–30 Gy in 10–15 fractions was considered for patients who responded to chemoimmunotherapy.
The primary endpoint was overall survival. Secondary endpoints included overall response rate, progression-free survival, and toxicity.
Enrollment Was Stopped Early for Futility and Safety Concerns
The trial began enrollment in January 2022 and was prematurely discontinued in September 2025 following recommendations from the independent Data and Safety Monitoring Committee. The decision was based on more serious adverse events in the thoracic radiotherapy group and futility.
By the time enrollment was stopped, 228 patients from 20 European hospitals had been randomized. The thoracic radiotherapy group included 115 patients, while the chemoimmunotherapy-alone group included 113 patients.
The median age was 68 years, with a range of 39 to 84 years. Women represented 50.4% of the study population. ECOG performance status 0 was reported in 37.7% of patients. Most patients had stage IV disease, accounting for 96.1% of the trial population. Liver metastases were present in 39.9%, and brain metastases were present in 28.1%.
The treatment groups were well balanced at baseline.
Patients received a mean of 3.6 chemoimmunotherapy courses. The mean number of total durvalumab courses was 7.5, with a range from 1 to 30. In the thoracic radiotherapy arm, 91.3% of patients received radiotherapy.
Thoracic Radiotherapy Did Not Improve Survival or Disease Control
The addition of thoracic radiotherapy did not improve overall survival.
Median overall survival was 10.0 months in the thoracic radiotherapy group compared with 11.1 months in the chemoimmunotherapy-alone group. The hazard ratio was 1.12, with a 95% confidence interval of 0.82–1.54, and the difference was not statistically significant.
Progression-free survival was also unchanged. Median progression-free survival was 5.1 months in both groups, with a hazard ratio of 1.09 and a 95% confidence interval of 0.83–1.44.
Overall response rates were nearly identical. The response rate was 88.5% in the thoracic radiotherapy group and 89.6% in the chemoimmunotherapy-alone group.
Together, these results show that adding thoracic radiotherapy after the first cycle of chemoimmunotherapy did not improve overall survival, progression-free survival, or response rate in this patient population.
Toxicity Was Higher With Thoracic Radiotherapy
Adverse events were more frequent among patients who received thoracic radiotherapy.
Overall adverse events occurred in 87.8% of patients in the thoracic radiotherapy group compared with 69.9% in the chemoimmunotherapy-alone group. However, grade 3–4 adverse events were not significantly increased, occurring in 21.1% versus 17.5%, respectively.
Esophagitis was a notable toxicity in the thoracic radiotherapy arm. It occurred in 47.8% of patients, with grade 3–4 esophagitis reported in 10.4%.
The trial also reported more deaths from causes other than SCLC in the thoracic radiotherapy group, occurring in 14.8% compared with 3.5% in the chemoimmunotherapy-alone group. When deaths occurring before thoracic radiotherapy commenced were excluded, the difference was no longer statistically significant, although numerically higher in the thoracic radiotherapy group.
Why This Matters
This phase III trial directly addresses an important question in extensive-stage SCLC: whether thoracic radiotherapy still adds value when patients are already receiving modern chemoimmunotherapy with durvalumab.
Although earlier evidence supported thoracic radiotherapy after chemotherapy in selected patients with extensive-stage SCLC, this study did not show a benefit when radiotherapy was added early to platinum/etoposide plus durvalumab. The absence of improvement in overall survival, progression-free survival, and response rate suggests that this strategy does not provide additional disease control in the studied population.
The safety findings are also clinically relevant. Thoracic radiotherapy increased the overall rate of adverse events and caused clinically meaningful esophagitis, including grade 3–4 esophagitis in more than one in ten patients in the radiotherapy arm.
These data suggest that routine addition of thoracic radiotherapy to first-line chemoimmunotherapy should not be considered beneficial for unselected patients with extensive-stage SCLC. The findings reinforce the need to carefully evaluate radiotherapy timing, patient selection, disease burden, and toxicity risk in future trials.
In this phase III study, concurrent thoracic radiotherapy with platinum/etoposide and durvalumab did not improve outcomes in extensive-stage SCLC and was associated with higher toxicity.
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