Pembrolizumab: first experience with recurrent primary central nervous system (CNS) tumors

Abstract

Patients with progressive primary brain tumors (PBT) are attracted to promising new treatments, even prior to convincing data. Anti-PD1 immunotherapies have been in the spotlight since publication of groundbreaking results for metastatic melanoma with pembrolizumab (PBL). Our objective was to report on the response and toxicity of PBL in patients with advanced PBT. We retrospectively reviewed the charts of 22 patients (17 adults and 5 children) with recurrent central nervous system tumors treated with PBL. We analyzed prior antineoplastic therapies, steroid usage, and outcomes. Patients received a median of two neoplastic therapies prior to PBL, and a median of three infusions of PBL in adults and four in children. Twelve patients (9 adults and 3 children) started PBL on steroids (median dose in adults 4 mg; range 2-8, and in children 1.5 mg, range 0.5-4) and five patients received steroids later during PBL treatment. Twelve patients (10 adults and 2 children) received concomitant bevacizumab with PBL. Side effects were minimal. All patients showed progressive tumor growth during therapy. Median OS from the start of PBL was 2.6 months in adults and 3.2 months in children. Two GB patients underwent tumor resection following treatment with PBL. Tumor-lymphocytic response in these cases was unremarkable, and PD-L1 immuno-staining was negative. In this series of 22 patients with recurrent primary brain tumors, PBL showed no clinical or histologic efficacy. We do not recommend further use of PBL for recurrent PBT unless convincing prospective clinical trial data are published.

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

“…On the other hand, there are also conflicting results. A recently published retrospective analysis of 22 patients with heavily pretreated refractory progressive primary brain tumors (including 10 with GBM) treated with pembrolizumab as a salvage agent in four major Israeli brain tumor centers showed only limited OS of no more than 3.2 months (139). The authors do not recommend further use of pembrolizumab for the recurrent primary brain tumors until convincing positive prospective clinical trial data is published.…”

Limitations and opportunities for immune checkpoint inhibitors in pediatric malignancies

“…Blumenthal et al reported their experience of pembrolizumab in patients with recurrent brain tumors including 5 pediatric patients, but they failed to show a benefit on overall survival [39]. The obvious exceptions are pediatric patients with refractory Hodgkin lymphoma (HL) which have shown durable responses to pembrolizumab [40,41].…”

“…Although clinical trials have shown tumor responses in some patients, few are major responses and most have not been durable [12,39–41]. There is a need to better understand the mechanisms of action of PD-1/PD-L1 in these pediatric tumors, to determine if there is an underlying genetic resistance to ICIs [13,96].…”

Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature

“…Pembrolizumab has proven safe and efficacious in the treatment of a host of diseases, including NSCLC [26][27][28][29], melanoma [26,30], malignant mesothelioma [31], Hodgkin lymphoma [32][33][34], urothelial cancer [35,36], breast cancer [37], and progressive primary brain tumors [38]. Pembrolizumab has rarely been utilized in the gynecologic setting; however, it has been reported to have a favorable safety profile and durable antitumor activity in cervical and endometrial cancer [39][40][41] as well as gestational trophoblastic neoplasia [42].…”