Apatinib  combined with temozolomide in the treatment of recurrent glioblastomas: an exploratory study

Abstract Background Glioblastoma (GBM) is the most common primary malignant brain tumor with poor prognosis. At present, there is no standard treatment for GBM who failed first-line treatment. Apatinib is a new type of oral small molecule angiogenesis inhibitor. The goals of this study are to research the curative effect, side effects and changes of immune factors and cytokines of treatment with Apatinib combined with TMZ (NCT:04253873). Methods 12 patients with recurrent GBM who failed first-line treatment were treated with apatinib combined with TMZ. They received oral apatinib (500 mg/day) in conjunction with TMZ (150 mg/m2/day). Contrast-enhanced MRI was performed every 4 weeks before and after treatment to measure the tumor volume. The peripheral blood samples were collected and the expressions of soluble PD-1(sPD-1), soluble PD-L1(sPD-L1), IL-6 and IL-10 in peripheral blood were detected by ELISA. Results The objective effective rate (ORR) was 41.67% (5/12). The disease control rate (DCR) was 75% (9/12). The median progression-free survival (m PFS) time was 6 months. The 6-month PFS rate was 50%. The most common adverse events were Hypertension and Fatigue. In our study, we did hematological analysis on 5 patients out of 12, we found that the plasma expression of sPD-L1 decreased and the expression of sPD-1 increased in the patients with significant reduced tumor volume, which may be related to longer survival and better prognosis, While the expressions of sPD-L1 increased and sPD-1 decreased in some patients with enlarged tumor volume, which may be related to shorter survival and worse prognosis. The expression levels of IL-6 and IL-10 in blood showed variation in patients with different tumor volume change. And the expression levels of △sPD-1, △sPD-L1, △IL-6 showed significant correlations to the tumor volume changes (△volume) (r=-0.651, p = 0.002; r = 0.898, p < 0.0001; r = 0.463, p = 0.040).The changes in △IL-10 were not correlated with tumor volume changes (△volume ) (r = 0.408, p = 0.074). Conclusion Apatinib combined with TMZ is safe and effective in the treatment of recurrent GBM. This study showed that immune factors (sPD-1, sPD-L1) may be potential prognostic biomarkers for GBM patients.