Continuous Low-Dose Apatinib Combined With WBRT Significantly Reduces Peritumoral Edema and Enhances the Efficacy of Symptomatic Multiple Brain Metastases in NSCLC.

BACKGROUND: Symptomatic multiple brain metastases with peritumoral brain edema (PTBE) occur in non-small cell lung cancer patients (NSCLC) who are without driver mutations or are resistant to epidermal growth factor tyrosine kinase (EGFR-TKI) are often associated with an unfavorable prognosis. Whole brain radiation therapy (WBRT) which comes with many complications and unsatisfactory effects, is the only option for the treatment. Previous studies have shown that bevacizumab can reduce the volume of PTBE and improve efficiency of radiotherapy. This study evaluated the effects and safety of apatinib combined with WBRT in NSCLC patients with symptomatic multiple brain metastases and PTBE. METHODS: We performed a retrospective review of 34 patients with symptomatic multiple brain metastases from NSCLC (number >4, and at least 1 measurable brain metastasis lesion with cerebral edema). Intracranial objective response rate (IORR), peritumoral edema and intracranial tumor volumetric measurement, Karnofsky performance status (KPS) and adverse events (AEs) were evaluated. Median intracranial progression-free survival (mIPFS) and median overall survival (mOS) were also analyzed. RESULTS: Thirteen cases received apatinib (125 mg or 250 mg, QD, oral) combined with WBRT and 21 cases received chemotherapy combined with WBRT were inclued. Apatinib combination group can better reduce the volume of intracranial tumors and PTBE and total steroid dosage used. It was associated with a better IORR (84.6% vs 47.6%, P = 0.067), longer mIPFS (6.97 vs 4.77months; P = 0.014). There was no significant difference in mOS(7.70 vs 6.67 months; P = 0.14) between the 2 groups. The most common adverse events of apatinib combination WBRT included grade 1/2 nausea (4/13), fatigue (3/13), hypertension (2/13) and white blood cell decrease (2/13). No grade 3/4 AEs were observed. CONCLUSION: Apatinib plus WBRT is well tolerated and may be a potential choice for relapsed or drug-resistant advanced NSCLC patients with symptomatic multiple brain metastases and PTBE.

Significant response of low-dose apatinib monotherapy in brain metastases of triple-negative breast cancer: A case report.

RATIONALE: The potential efficacy of apatinib in patients with advanced triple-negative breast cancer (TNBC) has been observed in a previous phase II clinical study. However, there is no study to evaluate its efficacy and safety in TNBC patients with brain metastasis (BM). Here we report one case that apatinib exhibited excellent antitumor effects in a breast cancer patient with brain metastasis, with no serious treatment-associated with adverse event. PATIENT CONCERNS: In this case report, one Chinese woman who was diagnosed with stage IV TNBC with multiple bone, lung, and brain metastases was unable to tolerate chemotherapy and refused whole-brain radiation therapy (WBRT) due to her poor physical condition. She had previously undergone radical mastectomy and intravenous chemotherapy. DIAGNOSES: Triple-negative breast cancer. INTERVENTIONS: The patient underwent left radical mastectomy with ipsilateral axillary lymph node dissection, and the following adjuvant chemotherapy, but developed multiple bone, lung, and brain metastases. Due to her poor physical condition, chemotherapy was not eligible for her. And she refused WBRT and chose to take low-dose apatinib (250 mg, oral, daily) monotherapy. OUTCOMES: After 2 months of treatment, the symptom of headache and vomiting relieved and all the brain metastases (BMs) lesions disappeared. LESSONS: Low-dose apatinib monotherapy may be an alternative treatment for patients with poor physical condition. Preclinical and clinical studies should be conducted to further evaluate the mechanism and efficacy of apatinib in the treatment of BM from TNBC, as well as to explore the optimal dose of the drug.