Long-Term Data Show Prophylactic Cranial Irradiation Prolongs DFS, Not OS, in Stage III NSCLC
A 10-year updated analysis of a phase 3 trial demonstrated that use of prophylactic cranial irradiation in NSCLC prolonged disease-free survival, but not overall survival.
|The following article features coverage from the International Association for the Study of Lung Cancer (IASLC) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.|
A 10-year updated analysis demonstrated no difference in overall survival (OS) among patients with locally advanced non-small cell lung cancer (NSCLC) who received prophylactic cranial irradiation (PCI) compared with those who were under observation alone — but the limited statistical power prevented a definitive conclusion about an overall survival benefit, according to results from a phase 3 trial presented at the IASLC's 19th World Conference on Lung Cancer in Toronto, Canada.1
Previous results from this trial showed that PCI prolonged disease-free survival (DFS) and reduced the number of brain metastases compared with observation. The purpose of this analysis was to determine if, after a decade following the conclusion of the trial, use of PCI prolonged OS.
The trial randomly assigned 340 patients with stage III NSCLC who did not progress after surgery and/or radiation therapy with or without concurrent chemotherapy. Patients treated with PCI received 30 Gy in 15 fractions. The primary endpoint was OS and the secondary endpoints included DFS, neurocognitive function, and quality of life.
There was no difference in OS between the PCI and observation arms during a median follow-up of 2.1 years for the entire cohort or 9.2 years for living patients (hazard ratio [HR], 1.23; 95% CI, 0.95-1.59; P = .12).
The authors noted that, “with the current data, there is only 45% power to detect the hypothesized difference HR = 1.25 at 1-sided significance level of 0.025,” suggesting that definitive conclusions on overall survival cannot be drawn from these data.
For patients who did not undergo surgery, however, PCI resulted in significantly prolonged survival compared with observation (HR, 1.42; 95% CI, 1.04-1.94; P = .026).
DFS remained improved with PCI compared with observation (HR, 1.32; 95% CI, 1.03-1.69; P = .03), including an analysis of nonsurgical patients (P = .014). Patients in the observation arm were 2.33 times more likely to develop brain metastases compared with individuals in the PCI arm (P = .004).
Although information on neurocognitive function across cohorts was previously published, suggesting that PCI did not significantly alter overall function at 1 year compared with observation, there was a trend for a larger decline.2 The PCI arm, however, demonstrated a significantly greater decline in the Hopkins Verbal Learning Test for immediate recall (P = .03) and delayed recall (P = .008) compared with observation. There were insufficient data to evaluate neurocognitive function in this 10-year updated analysis.
The authors concluded that these data indicate that PCI “continued to significantly improve DFS and reduce brain metastases,” but noted that the study was inadequately powered to detect OS.
Read more of Cancer Therapy Advisor's coverage of the IASLC 2018 meeting by visiting the conference page.
- Sun A, Hu C, Gore E, et al. 10-year updated analysis of NRG Oncology/RTOG 0214: a phase III comparison of PCI vs. observation in patients with LA-NSCLC. Presented at: International Association for the Study of Lung Cancer 19th World Conference on Lung Cancer; September 23-26, 2018; Toronto, Canada. Abstract OA01.01.
- Sun A, Bae K, Gore EM, et al. Phase III trial of prophylactic cranial irradiation compared with observation in patients with locally advanced non-small-cell lung cancer: neurocognitive and quality-of-life analysis. J Clin Oncol. 2011;29(3):279-286.