CHICAGO, IL—Prophylactic cranial irradiation (PCI) did not show an overall survival (OS) benefit when used in patients with extensive disease-small cell lung cancer (ED-SCLC) who had a confirmed absence of brain metastases, a phase 3 trial concluded at the 2014 American Society of Clinical Oncology (ASCO) Annual Meeting.
Following a preplanned interim analysis in July 2013 of survival data of 163 patients from 41 centers, the study was terminated because of futility, reported Takashi Seto, MD, PhD, of the Department of Thoracic Oncology at National Kyushu Cancer Center in Fukuoka, Japan.
Previously, PCI was shown to reduce the risk of brain metastases and prolong OS in patients with ED-SCLC. However, that study raised several concerns, including lack of magnetic resonance imaging (MRI) assessment to confirm absence of brain metastases prior to enrollment, use of induction chemotherapy other than platinum, and variations in the radiation doses, Dr. Seto said.
This study randomly assigned patients with ED-SCLC who had any response to first-line platinum doublet chemotherapy and confirmed absence of brain metastases by MRI to PCI 25 Gy in 10 fractions or to observation alone. Primary endpoint was OS; secondary endpoint included time to brain metastases (evaluated every 3 months by imaging), progression-free survival (PFS), and safety.
At study termination, median follow-up was 9.4 months and 111 deaths had been observed, he noted. Median OS was 10.1 months (range, 8.5-13.2 months) for the PCI arm (n=84) and 15.1 months (range, 10.2-18.7 months) for the observation-alone arm (n=79; hazard ratio [HR], 1.38; 95% CI: 0.95-2.02; stratified log-rank test, P = 0.091). The Bayesian predictive probability of showing superiority of PCI over observation alone was 0.01%.
At 12 months, time to brain metastases was significantly reduced by PCI compared with observation alone, 32.4% versus 58.0% (Gray’s test, P < 0.001). However, median PFS was comparable between the two arms (2.2 vs. 2.4 months; HR, 1.12; 95% CI: 0.82-1.54).
No significant difference in adverse events greater than grade 2 was observed between the two arms, Dr. Seto concluded.
The discussant for this presentation, Walter John Curran, MD, of The Winship Cancer Institute of Emory University, Atlanta, GA, said that showing a reduction in brain metastases without an OS benefit is a “very biologic plausible result.” He added that determining how PCI can be delivered with a better risk/benefit ratio is the subject of ongoing studies.
- Seto T, Takahashi T, Yamanaka T et al. Abstract 7503. Presented at: 2014 American Society of Clinical Oncology (ASCO) Annual Meeting; May 30-June 3, 2014; Chicago, IL.