Treatment of MGMT promoter unmethylated glioblastoma with PD-1 inhibitor combined with anti-angiogenesis and epidermal growth factor receptor tyrosine kinase inhibitor: a case report

Glioblastoma (GBM) is the most common primary central nervous system (CNS) malignancy in adults and is associated with poor prognosis, especially even worse in those with unmethylated MGMT promoter. Currently, maximal safe resection combined with temozolomide (TMZ) concurrent chemoradiotherapy and TMZ adjuvant chemotherapy has been considered the standard treatment for newly diagnosed GBM. The efficacy of drugs other than TMZ is currently undefined. With increasing understanding of the biological characteristics of GBM, more and more studies are being conducted on drug targets, such as specific signaling pathways and microenvironment. Herein, we report the case of a GBM patient with unmethylated MGMT promoter who was intolerant to TMZ, and underwent treatment with the combination of carelizumab, anlotinib, and oxitinib during radiotherapy according to results of wholeexome sequencing (WES) and the patient's condition. The progression-free survival (PFS) and overall survival (OS) for this case were respectively nearly 11 and 18 months, significantly exceeding the historical data and the tolerance of the treatment for this case without sever adverse effects was favorable. Our case provides clinical evidence supporting the efficacy of the above three drugs and radiotherapy, which may translate into novel individualized treatment strategies for GBM patients who are intolerant to TMZ.

Automated summary

GBM is the most common primary CNS malignancy in adults, with standard treatment being maximal safe resection combined with chemoradiotherapy and adjuvant chemotherapy. A treatment regimen combining carelizumab, anlotinib, and oxitinib shows promising efficacy for patients intolerant to TMZ.