Prophylactic Cranial Irradiation Reduces Brain Metastases and Improves Overall Survival in High-Risk Metastatic Non-Small Cell Lung Cancer Patients: A Randomized phase 2 Study (PRoT-BM trial).

PURPOSE:To date, studies regarding the use of prophylactic cranial irradiation (PCI) versus standard of care (SoC) for patients with non-small cell lung cancer (NSCLC) have not shown a significant effect in terms of overall survival (OS). Additionally, the effect of PCI among high-risk patients has been scarcely studied. The objective of this randomized phase 2 study was to evaluate the role of PCI in a population of patients at high risk for development of brain metastases (BM). METHODS AND MATERIALS:Eligible patients had histologically confirmed NSCLC without baseline BM, harboring epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels at the time of diagnosis. Participants received systemic therapy according to molecular status, those without progressive disease were then assigned to receive SoC or SoC + PCI (25 Gy in 10 fractions). The primary outcome was cumulative incidence of brain metastases (CBM). The secondary endpoints included progression-free survival and OS. Quality of life and neurocognitive function are discussed in a separate article (Clinicaltrials.gov: NCT01603849). RESULTS:From May 2012 to December 2017, 84 patients were enrolled in the study, with 41 patients allocated to receive PCI and 43 received SoC. Patients allocated to receive PCI had a CBM at 24 months of 7% versus 38% in those allocated to the SoC arm. PCI was associated with a hazard ratio of 0.12 (95% confidence interval, 0.035-0.42) for developing BM. A benefit in OS was also observed (64.5 vs 19.8 months; hazard ratio: 0.41 (95% confidence interval, 0.22-0.78; P =∙007). CONCLUSIONS:Among a selected population at high risk for developing BM, PCI significantly decreased CBM in addition to increasing progression-free survival and OS. To our knowledge, this is the first study to evaluate PCI in epidermal growth factor receptor mutations, anaplastic lymphoma kinase rearrangements, or elevated carcinoembryonic antigen levels in patients with NSCLC, showing a significant improvement in CBM. This relevant information should be of particular importance in the context of patients without access to third-generation targeted agents. Further studies are warranted to ascertain this effect.