European Phase III Trial Suggests Benefit of Thoracic Radiotherapy in Extensive-Stage Small Cell Lung Cancer
In a European phase III trial reported in The Lancet, Slotman et al found benefits of thoracic radiotherapy in patients with extensive-stage small cell lung cancer who had responded to chemotherapy and had received prophylactic cranial radiotherapy. Although thoracic radiotherapy did not significantly improve 1-year overall survival, the primary endpoint, significant improvements were observed in overall survival at 2 years and in progression-free survival.
In the trial, 495 patients from 42 hospitals in the Netherlands, UK, Norway, and Belgium with World Health Organization performance status of 0 to 2 were randomly assigned between February 2009 and December 2012 to receive thoracic radiotherapy at 30 Gy in 10 fractions (n = 247) or no thoracic radiotherapy (n = 248). The mean time between diagnosis and randomization was 17 weeks. Analysis of outcomes was in the intent-to-treat population.
Overall Survival
Median follow-up was 24 months. Overall survival at 1 year was 33% (95% confidence interval [CI] = 27%–39%) in the thoracic radiotherapy group vs 28% (95% CI = 22%–34%) in the control group (hazard ratio [HR] = 0.84, P = .066). Overall survival at 2 years was 13% (95% CI = 9%–19%) vs 3% (95% CI = 2%–8%; P = .004). Median overall survival was 8 months in both groups. Subgroup analysis for 1-year overall survival showed no significant differences between treatment groups.
Progression
Median progression-free survival was 4 months vs 3 months (HR = 0.73, P = .001), and 6-month progression-free survival was 24% (95% CI = 19%–30%) vs 7% (95% CI = 4%–11%; P = .001). Isolated intrathoracic progression occurred in 20% vs 46% (P < .0001), intrathoracic progression with or without progression elsewhere occurred in 44% vs 80% (P < .0001), brain metastases occurred in 9.7% vs 5.2% (P = .09), and progression at other sites occurred in 60% vs 40% (P < .0001).
Toxicity
No severe toxic effects were observed. Only one grade 4 adverse event (fatigue in a control patient) was observed. The most common grade 3 adverse events in the radiotherapy group were fatigue (4.5% vs 3.2%), esophagitis (1.6% vs 0%), dyspnea (1.2% vs 1.6%), insomnia (1.2% vs 0.8%), and headache (1.2% vs 0.8%).
The investigators concluded: “Thoracic radiotherapy in addition to prophylactic cranial irradiation should be considered for all patients with [extensive-stage small cell lung cancer] who respond to chemotherapy.”
Ben J. Slotman, MD, of VU University Medical Center, Amsterdam, is the corresponding author for The Lancet article.
The study was funded by the Dutch Cancer Society, Dutch Lung Cancer Research Group, Cancer Research UK, Manchester Academic Health Science Centre Trials Coordination Unit, and UK National Cancer Research Network. The study authors reported no potential conflicts of interest.
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