Recurrent glioma clinical trial, CheckMate-143: the game is not over yet
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Anna C. Filley1, Mario Henriquez1 and Mahua Dey1
1Department of Neurosurgery, Indiana University Purdue University Indianapolis, Indianapolis, Indiana, USA
Mahua Dey, email: [email protected]
Keywords: gliolastoma, checkpoint inhibitor, PD-1/PD-L1, malignant glioma, immunotherapy
Received: July 13, 2017 Accepted: September 08, 2017 Published: October 06, 2017
Glioblastoma (GBM) is the most common, and aggressive, primary brain tumor in adults. With a median patient survival of less than two years, GBM represents one of the biggest therapeutic challenges of the modern era. Even with the best available treatment, recurrence rates are nearly 100% and therapeutic options at the time of relapse are extremely limited. Nivolumab, an anti-programmed cell death-1 (PD-1) monoclonal antibody, has provided significant clinical benefits in the treatment of various advanced cancers and represented a promising therapy for primary and recurrent GBM. CheckMate 143 (NCT 02017717) was the first large randomized clinical trial of PD pathway inhibition in the setting of GBM, including a comparison of nivolumab and the anti-VEGF antibody, bevacizumab, in the treatment of recurrent disease. However, preliminary results, recently announced in a WFNOS 2017 abstract, demonstrated a failure of nivolumab to prolong overall survival of patients with recurrent GBM, and this arm of the trial was prematurely closed. In this review, we discuss the basic concepts underlying the rational to target PD pathway in GBM, address implications of using immune checkpoint inhibitors in central nervous system malignancies, provide a rationale for possible reasons contributing to the failure of nivolumab to prolong survival in patients with recurrent disease, and analyze the future role of immune checkpoint inhibitors in the treatment of GBM.
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