Prophylactic cranial irradiation improved DFS and decreased brain metastasis rates at 5 and 10 years compared with observation among patients with stage III locally advanced non-small cell lung cancer, according to results of a randomized phase 3 trial published in JAMA Oncology.
The treatment, however, did not improve OS, the study’s primary outcome. But, researchers noted that the reason for this result could be poor patient accrual. The original aim was to enroll 1,058 participants, but total accrual at study closing was only 356, including 16 patients who were deemed ineligible or withdrew consent.
“As the incidence of brain metastases rises in patients living longer with improved control of loco-regional and distant disease, the need to establish an accepted means of prevention of brain metastases remains important,” Alexander Sun, MD, of the department of radiation oncology at Princess Margaret Cancer Centre and lead study author, said in a press release. “Researchers need to identify the appropriate patient population and a safe intervention on future trials.”
Prophylactic cranial irradiation (PCI) is standard of care to prevent brain metastases after initial therapy among patients with small cell lung cancer. PCI also has been shown to reduce incidence of brain metastases in patients with NSCLC, but its impact on survival among this patient population is unknown.
Sun and colleagues analyzed 340 patients (mean age, 61 years; 213 men) with stage III NSCLC randomly assigned to PCI (n = 163) or observation (n = 177).
OS served as the primary endpoint. DFS and incidence of brain metastasis served as secondary endpoints.
By the time of analysis, 277 patients had died, primarily due to their lung cancer.
Median follow-up was 2.1 years for all patients and 9.2 years for surviving patients.
Results showed no significant improvement in OS among patients who received PCI vs. observation at 5 years (24.7% vs. 26%) and at 10 years (17.6% vs. 13.3%), resulting in an HR of 0.82 (95% CI, 0.63-1.06).
However, patients who underwent PCI demonstrated higher rates of DFS (5-year, 19% vs. 16.1%; 10-year, 12.6% vs. 7.5%; HR = 0.76; 95% CI, 0.59-0.97) and lower rates of brain metastases at 5 and 10 years (16.7% vs. 28.3% at both time points; HR = 0.43; 95% CI, 0.24-0.77).
These data indicated patients in the PCI group were 57% less likely to develop brain metastases than patients in the observation group.
Among a subgroup of 225 patients who did not undergo surgery on the primary lung tumor, those who received PCI vs. observation demonstrated significantly longer median OS (2.3 years vs. 1.9 years; P = .027). Multivariable analysis within this subgroup indicated PCI may effectively extend OS and DFS and reduce brain metastases.
“If the planned sample size had been accrued, then there may have been enough statistical power to detect the hypothesized effect size in OS, as the observed magnitude was numerically similar to the hypothesized,” Sun and colleagues wrote. “This study ... is currently part of an international collaborative effort, which is performing an individual patient data meta-analysis of similar randomized studies. It is hoped that this meta-analysis will have the power to detect an OS advantage for PCI, as was the case for the establishment of PCI in [small cell lung cancer].” – by John DeRosier
Disclosures: Sun reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.