Case report: The effective response to pembrolizumab in combination with bevacizumab in the treatment of a recurrent glioblastoma with multiple extracranial metastases

Abstract

Multiple extracranial metastases of recurrent glioblastoma are rare and often indicate a very poor prognosis. The main conventional treatments are chemotherapy, radiotherapy, chemoradiotherapy or antiangiogenic therapy. Median overall survival is 2.3 to 6 months after the detection of extracranial metastases, and to date, there is no effective treatment for these patients. Herein, we report a recurrent glioblastoma patient with lung metastasis treated with a combination therapy containing bevacizumab and pembrolizumab due to overexpression of PD-L1 and the absence of driver mutations. The progression-free survival was 11 months from lung metastases to bone metastases. This combination treatment was further used as maintenance therapy for another 11 months after bone metastasis and secondary dorsal metastasis because there was no suitable treatment alternative. The overall survival was 27 months after lung metastases, which is much longer than previously reported cases. To our knowledge, this was the first effective use of bevacizumab plus pembrolizumab in a glioblastoma patient with extracranial metastases. Furthermore, this was the first time that bevacizumab plus pembrolizumab was used as a maintenance treatment in glioblastoma, with 11 months of response. Importantly, we showed that such combination therapy may be a novel and effective therapy for glioblastoma patients with extracranial metastases.

Metastatic glioblastoma to the lungs: a case report and literature review

“…Treatment for metastatic glioblastoma is challenging and no standard treatment exists [ 11 , 72 , 73 ]. Therapeutic options gleaned from existing literature includes bevacizumab, surgery, temozolomide rechallenge, etoposide, irinotecan, procarbazine and immunotherapy [ 12 , 72 , 74 , 75 ]. Despite bevacizumab and lomustine, our patient developed metastatic glioblastoma to the lungs.…”

“…Despite bevacizumab and lomustine, our patient developed metastatic glioblastoma to the lungs. In a similar case of metastatic glioblastoma to the lungs, Yang et al reported a prolonged response of 27 months with combined bevacizumab and pembrolizumab [ 72 ]. The addition of pembrolizumab to bevacizumab was considered for our patient, but transport barriers from her rehabilitation facility restricted any intravenous therapy.…”

The efficacy and adverse events of bevacizumab combined with temozolomide in the treatment of glioma: a systemic review and meta-analysis of randomized controlled trials

“…As early as 2007, a Duke University trial of BEV combined with irinotecan in the treatment of recurrent malignant glioma showed that BEV combined with other drugs could lead to better therapeutic benefits ( 34 ). Subsequently, various studies combined BEV with multiple drugs to explore the optimal drug dose and frequency of treatment ( 35–37 ). This suggests that BEV has great potential for the treatment of glioblastoma, combining with TMZ in the treatment of glioma results in a stronger therapeutic effect.…”

Pediatric H3K27M‑mutant diffuse midline glioma with vertebral metastasis: A case report and literature review

“…Drugs targeting vascular endothelial growth factor and epidermal growth factor receptor, as well as anti-angiogenic and several multi-kinase inhibitors, have not exhibited satisfactory efficacy (31)(32)(33). However, programmed cell death-ligand 1/programmed cell death-1 inhibitors may be a beneficial treatment option for such patients (34).…”