Randomized trial on thoracic radiotherapy (TRT) in extensive-stage small cell lung cancer.

Abstract

Background: Prophylactic cranial irradiation (PCI) reduces the risk of brain metastases and improves survival in ES‐SCLC after response to chemotherapy. As a majority of patients have intrathoracic disease after chemotherapy, this randomized study assesses the role of TRT in ES‐SCLC. Methods: Patients (WHO 0‐2) with confirmed ES‐SCLC with a response after 4‐6 cycles of standard chemotherapy were randomized to receive TRT (30 Gy/10fx) or no TRT. All received PCI. Primary study endpoint was overall survival. Acute toxicity was graded using CTCAE v3.0. The study had 80% power to detect a hazard ratio of 0.76 at 1 year (2‐sided 5% signif.). Accounting for 5% dropout before treatment, 483 patients had to be randomized. Analysis was based on intent to treat. Results: Between Feb'09 and Dec'12, 498 patients were enrolled (249 per arm); Median follow‐up was 24 months. 88% had residual intrathoracic disease. Baseline characteristics were well balanced. Mean age was 63 year (range 36‐85), 89% had WHO 0‐1; 11% WHO2. Mean interval between start of chemotherapy and randomization was 16 weeks. Three patients subsequently withdrew informed consent leaving 247 (TRT) versus 248 patients (control arm). In the TRT arm, 5 patients did not receive TRT due to progression or refusal. No severe toxicities were observed. At the time of analysis (Dec'13), 76 patients were still alive. Progression‐free survival was longer in the TRT‐arm (HR=0.73, CI 0.61‐0.87; p=0.001). Curves for overall survival overlapped during the first 9 months and then diverged in favour of the TRT‐arm. The survival difference at 1 year was not statistically significant (33% vs 28%; HR=0.84, CI 0.69‐1.01; p=0.066). Survival at 2 years was 13% (CI 9‐19) for the TRT and 3% (CI 2‐8%) for the control arm (P=0.004). Conclusions: TRT improves progression‐free survival. Although TRT did not influence the risk of death in the first year, it led to a significant increase in 2‐year survival. TRT should therefore be offered to all ES‐SCLC patients with a response to initial chemotherapy.