PL01.5.A NEOADJUVANT CAMRELIZUMAB AND APATINIB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS:PRIMARY REPORT OF AN OPEN LABEL PHASE II STUDY

Abstract

Abstract BACKGROUND Recurrent high-grade gliomas (HGG) is a challenge with a poor prognosis and limited treatment options. A study has reported that neoadjuvant immunotherapy upregulates PD-L1 expression and CD8+T cell infiltration, which is expected to improve the survival of HGG. Our study (NCT04588987) aimed to assess the efficacy and safety of perioperative camrelizumab (anti-PD-1 antibody) and apatinib (antiangiogenic agent) in patients with recurrent HGG. METHODS Patients with recurrent HGG received 14 days of neoadjuvant treatment with camrelizumab (intravenous injection 200 mg on day 1) and apatinib (oral 250 mg per day on days 1-7), followed by surgery for recurrent tumor. Sequential therapy began 2 weeks after surgery with the biweekly camrelizumab (200mg) and 4 weeks after surgery with the daily apatinib (250mg) until investigator-assessed progressive disease or unable to tolerate toxicity. The primary endpoint was overall survival (OS). RESULTS Between Oct 9, 2020 and Feb 14, 2023, 18 patients have been enrolled (14 for recurrent glioblastomas, 3 for anaplastic astrocytoma and 1 for anaplastic oligodendroglioma). At the data cut-off (Mar 31, 2023), 16 patients discontinued study treatment (12 cases of disease progression, 1 case of liver function injury, 1 case of COVID-19 infection, 1 case refused treatment and 1 case died before progression). The median treatment time for camrelizumab and apatinib were 4.8 (95% CI: 3.8-5.9) months and 5.2 (95% CI: 3.9-6.4) months, respectively. The median OS was 12.9 months (95% CI: 9.3-16.4) with a median follow-up time of 17.5 (95%CI:9.0-26.1) months. The median PFS was 4.8 months (95% CI: 4.4-5.2). Nine (50%) patients occurred grade 3 treatment-related adverse events (TRAEs). Decreased lymphocyte count (22.2%, 4/18), hypertension (16.7%,3/18) and Increased aspartate aminotransferase (11.1%,2/18) were the most common grade 3 TRAEs, and there were no grade 4 or 5 TRAEs. CONCLUSION This combination therapy in recurrent HGG demonstrated encouraging efficacy, and TRAEs are manageable.Keywords: Apatinib, Camrelizumab, Neoadjuvant therapy, Recurrent high-grade gliomas.