Concurrent apatinib and brain radiotherapy in patients with brain metastases from driver mutation-negative non-small-cell lung cancer: study protocol for an open-label randomized controlled trial

Abstract Brain radiotherapy (BR) is a well-recognized approach for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC). However, the prognosis for these patients remains poor. Apatinib, an antiangiogenic agent targeting vascular endothelial growth factor receptor-2 has shown excellent efficacy in multiple solid tumors. This phase II (WWW. ClinicalTrials.gov Identifier: VEGFR-2 NCT03801200) randomized trial aims to evaluate the efficacy and safety of this combined modality paradigm in patients with BMs from driver mutation-negative NSCLC. This is a multicenter, open-label, randomized controlled clinical trial. A total of 90 eligible patients will be allocated in a 1:1 ratio, to either the experimental group (concurrent apatinib and BR) or the control group (BR alone). The primary endpoints is intracranial progression-free survival (iPFS). The secondary endpoints include intracranial objective response rate (ORR), intracranial disease control rate (DCR), intracranial time to progression (ITTP), overall survival (OS), and occurrence of peritumoral brain edema (PTBE) using standardized measurement. Quality of life and adverse events will also be evaluated. Assessments will be carried out before enrollment (baseline) along with 4 and 12 weeks after radiotherapy, followed by every 12 weeks thereafter and up to 24 months. In summary, the aim of this trial is to demonstrate the clinical efficacy and safety of concurrent BR and apatinib in driver mutation-negative NSCLC patients with multiple BMs, in efforts to expand management options for this population with poor prognosis.