Congress of Neurological Surgeons systematic review and evidence-based guidelines update on the role of targeted therapies and immunotherapies in the management of progressive glioblastoma.

Evan Winograd,Jeffrey J Olson,D Ryan Ormond,Isabelle Germano,Patrick Wen

doi:10.1007/s11060-021-03876-7

Abstract

The following questions and recommendations are pertinent to the following:Target populationThese recommendations apply to adults with progressive GBM who have undergone standard primary treatment with surgery and/or chemoradiation.Question 1In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationLevel III: Treatment with bevacizumab is suggested in the treatment of progressive GBM, as it provides improved disease control compared to historical controls as measured by best imaging response and progression free survival at 6 months, while not providing evidence for improvement in overall survival.Question 2In adults with progressive glioblastoma is the use of bevacizumab as combination therapy with cytotoxic agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationLevel III: There is insufficient evidence to show benefit or harm of bevacizumab in combination with cytotoxic therapies in progressive glioblastoma due to a lack of evidence supporting a clearly defined benefit without significant toxicity.Question 3In adults with progressive glioblastoma is the use of bevacizumab as a combination therapy with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 4In adults with progressive glioblastoma is the use of targeted agents as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 5In adults with progressive glioblastoma is the use of targeted agents in combination with cytotoxic therapies superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 6In adults with progressive glioblastoma is the use of immunotherapy monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 7In adults with progressive glioblastoma is the use of immunotherapy in combination with targeted agents superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.Question 8In adults with progressive glioblastoma is the use of immunotherapy in combination with bevacizumab superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?RecommendationThere is insufficient evidence to support a recommendation regarding this question.

Highlights

In 2014, guidelines for the management of progressive glioblastoma and the role of targeted therapies were published by the Association of Neurological Surgeons (AANS) and Congress of Neurological Surgeons (CNS) [1]
Question 1 In adults with progressive glioblastoma is the use of bevacizumab as monotherapy superior to standard salvage cytotoxic chemotherapy as measured by progression free survival and overall survival?
PFS6 15% for combination therapy, 18% monotherapy median PFS 3.5 m for both median OS 6.9 m combination, 7.5 m mono Toxicity: most common—fatigue, anemia, neurological symptoms/signs, hypertension, nausea, thrombocytopenia, constipation. 2 deaths, one to ICH, another to bowel perforation, both on combo therapy Authors’ conclusions: In summary, we did not find that the combination of bevacizumab and chemotherapy resulted in additional PFS or OS benefit compared with bevacizumab monotherapy in progressive GBM

Summary

Introduction

In 2014, guidelines for the management of progressive glioblastoma and the role of targeted therapies were published by the AANS and CNS [1]. We present the updated set of data and studies regarding targeted therapies as well as immunotherapy with and without targeted therapies. The median overall survival for a patient with newly diagnosed glioblastoma remains 14.6 months [2]. While cytotoxic therapies have long been used to treat malignancy, more recent attempts utilizing therapies targeting tumor progression and growth pathways, anti-angiogenic agents designed to target neovascular proliferation pathways, and immunotherapies aimed at utilizing a patient’s immune system to attack tumor cells have been studied. We present a systematic review and evidence-based practice guideline to help practicing physicians to determine the role of these treatments in progressive glioblastoma

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