The purpose of this study is to evaluate the efficacy and safety of concurrent radiotherapy with Apatinib in patients with Brain Metastases from drive gene wide-type Non-small-cell Lung Cancer (NSCLC).
Brain metastases (BM) develop in 22-54% of NSCLC patients during the disease course. NSCLC patients with BM with a median overall survival (OS) of 2-3 months when treated with systemic corticosteroid alone, and a median OS of 3-6 months when treated with whole brain radiation therapy (WBRT). Recently, several studies have reported the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for EGFR mutation NSCLC patients with BM. The median OS of EGFR mutation patients with BM significantly improved with TKIs treatment, which ranged from 11.8 to 18.8 months. However, for the EGFR wide-type NSCLC patients with BM, the prognosis remains poor. It was found that the combination of anti-VEGF drugs and brain radiotherapy can not only reduce the volume of peritumoral brain edema (PTBE), reduce the intracranial pressure, relieve the symptoms of nerve compression, reduce the risk of brain hernia during brain radiotherapy, and but also inhibit the hypoxia of tumor cells, increase the radiosensitivity of tumor cells, and ultimately improve the efficacy of radiotherapy. Apatinib, a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor (VEGFR) and mildly inhibits c-Kit and c-SRC, has been reported to show efficacy among some patients with malignant supratentorial gliomas. Therefore, the investigators initiated this study to evaluate the efficacy and safety of concurrent radiotherapy with Apatinib in patients with Brain Metastases from drive gene wide-type Non-small-cell Lung Cancer (NSCLC).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
radiotherapy with Apatinib
Hubei Cancer hospital
Wuhan, Hubei, China
Intracranial progression-free survival (iPFS)
Defined as the time from randomisation to progression of intracranial disease or death from any cause.
Time frame: Evaluated in 24 months since the treatment began
Disease control rate (DCR)
Proportion of patients with reduction or keeping in stable in tumor burden of a predefined amount
Time frame: 4 weeks after Radiotherapy.
Objective response rate (ORR)
Proportion of patients with reduction in tumor burden of a predefined amount
Time frame: 4 weeks after Radiotherapy.
intracranial time to progress (ITTP)
Defined as the time from randomisation to progression of intracranial disease
Time frame: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Overall survival (OS)
Defined as the time from randomisation to death from any cause
Time frame: Tumor assesment at 4 weeks and 12 weeks after radiotherapy, and then every 12 weeks, up to 24 months
Rate of Peritumoalbrainedema (PTBE)
PTBE volume was measured in a similar manner by measuring the high SI region in T2WI that was clearly distinguished from normal tissues, including the tumor. Edema index was calculated by dividing the PTBE volume by tumor volume. The Edema index represents the degree of the PTBE, compared to tumor volume, with an index of 1.0 indicating no PTBE development.
Time frame: 4 weeks after Radiotherapy.
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