The Effect of Prophylactic Cranial Irradiation (Pci) in the Patients with Extensive-Disease Small-Cell Lung Cancer (Ed-Sclc): Results of a Japanese Randomized Phase III Trial

Aim: A previous study has shown that PCI reduced the risk of brain metastases (BM) and prolonged the overall survival (OS) of patients with ED-SCLC (Slotman B et al, NEJM 2007). There were, however, several concerns that arose in association with that study, including the lack of magnetic resonance imaging (MRI) assessment to confirm the absence of BM before enrollment, the use of induction chemotherapy other than platinum, and variations in the radiation doses. The aim of this study is to assess the efficacy and safety of the PCI in the patients with ED-SCLC. Methods: From March 2009, patients with ED-SCLC who had any response to first-line chemotherapy (platinum agent plus irinotecan or etoposide) were randomized to either PCI (25Gy/10 fractions) or observation (Obs) alone. The patients were required to prove the absence of BM by MRI prior to enrollment. The primary endpoint was OS and a planned sample size of 330 was determined to detect the hazard ratio (HR) of 0.75 at a significance level of 0.05 and a power of 80%. Secondary endpoints included time to BM, progression-free survival (PFS), and adverse effects (AEs). Results: In July 2013, a preplanned interim analysis was conducted for the survival data of 163 pts from 41 centers. The study was terminated because of futility; with a median follow-up of 9.4 months and 111 observed deaths, the median OS was 10.1 and 15.1 months for PCI (n=84) and Obs (n=79), respectively (HR=1.38, 95%CI= 0.95-2.01; stratified log-rank test, P=0.091). Bayesian predictive probability of showing superiority of PCI over Obs was 0.01%. PCI significantly reduced the risk of BM as compared to Obs (32.4% vs 58.0% at 12 months; Gray's test, P Conclusions: PCI after response to chemotherapy might have a negative impact on OS in pts with ED-SCLC. Updated safety data will be presented at the conference. Disclosure: All authors have declared no conflicts of interest.