Glioblastoma is the most frequent and aggressive form among malignant central nervous system primary tumors in adults. Standard treatment for newly diagnosed glioblastoma consists in maximal safe resection, if feasible, followed by radiochemotherapy and adjuvant chemotherapy with temozolomide; despite this multimodal treatment, virtually all glioblastomas relapse. Once tumors progress after first-line therapy, treatment options are limited and management of recurrent glioblastoma remains challenging. Loco-regional therapy with re-surgery or re-irradiation may be evaluated in selected cases, while traditional systemic therapy with nitrosoureas and temozolomide rechallenge showed limited efficacy. In recent years, new clinical trials using, for example, regorafenib or a combination of tyrosine kinase inhibitors and immunotherapy were performed with promising results. In particular, molecular targeted therapy could show efficacy in selected patients with specific gene mutations. Nonetheless, some molecular characteristics and genetic alterations could change during tumor progression, thus affecting the efficacy of precision medicine. We therefore reviewed the molecular and genomic landscape of recurrent glioblastoma, the strategy for clinical management and the major phase I-III clinical trials analyzing recent drugs and combination regimens in these patients.
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Conflicts of Interest: A.I. declares research grants and travel funding from Carthera, research grants from Transgene, research grants from Sanofi, research grants from Air Liquide, research grants from Nutritheragene and travel funding from Leo Pharma, the Advisory board for Novocure and Leo Pharma. the authors declare no conflict of interest. V.Z. declares consulting or advisory role funding from Bristol-Myers Squibb and Merck, speakers’bureau funding from Bayer, Roche, Bristol-Myers Squibb, Astellas Pharma, Servier, AstraZeneca and Lilly, travel and accommodation funding from Bayer, Roche and Servier. G.L. declares consulting or Advisory Role funding from Bayer, AbbVie, Orbus Therapeutics and BrainFarm; travel funding from Roche and Bayer.
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