A Japanese phase III trial has shown no survival benefit of prophylactic cranial irradiation vs observation in patients with extensive-disease small cell lung cancer who had any response to platinum-based doublet chemotherapy and no brain metastases at baseline. These findings were reported in The Lancet Oncology by Takahashi et al. Nobuyuki Yamamoto, MD, of Wakayama Medical University, is the corresponding author of this article.
Nobuyuki Yamamoto, MD
In the open-label trial, 224 patients from 47 sites who had no brain metastases on magnetic resonance imaging (MRI) were randomized between April 2009 and July 2013 to receive prophylactic cranial irradiation at 25 Gy in 10 daily fractions of 2.5 Gy (n = 113) or observation (n =111). MRI was performed at 3-month intervals up to 12 months and at 18 and 24 months after enrollment. The primary endpoint was overall survival in the intent-to-treat population.
No Survival Benefit
On the basis of a planned interim analysis in June 2013 among the first 163 patients, the study was terminated early for futility. In the final analysis, median overall survival was 11.6 months in the prophylactic cranial irradiation group and 13.7 months in the observation group (hazard ratio [HR] = 1.27, P = .094). Brain metastases were found in 48% vs 69% of patients (P < .0001). Median progression-free survival was 2.3 months vs 2.4 months (P = .75). Radiotherapy for brain metastases was given to 46% vs 83% of patients who developed brain metastases. Second-line chemotherapy was given to 88% vs 89% of patients.
The most common grade ≥ 3 adverse events at 3 months were anorexia (6% in the prophylactic cranial irradiation group vs 2% in the observation group), malaise (3% vs < 1%), and muscle weakness in a lower limb (< 1% vs 5%). No treatment-related deaths were observed.
The investigators concluded: “In this Japanese trial, prophylactic cranial irradiation did not result in longer overall survival compared with observation in patients with extensive-disease small-cell lung cancer. Prophylactic cranial irradiation is therefore not essential for patients with extensive-disease small-cell lung cancer with any response to initial chemotherapy and a confirmed absence of brain metastases when patients receive periodic MRI examination during follow-up.” ■