Clinical utility of targeted next-generation sequencing assay in IDH-wildtype glioblastoma for therapy decision-making

• Published in: Neuro-oncology (Charlottesville, Va.) Va.), 2022-07, Vol.24 (7), p.1140-1149
• Main Authors: Lim-Fat, Mary Jane, Youssef, Gilbert C, Touat, Mehdi, Iorgulescu, J Bryan, Whorral, Sydney, Allen, Marie, Rahman, Rifaquat, Chukwueke, Ugonma, McFaline-Figueroa, J Ricardo, Nayak, Lakshmi, Lee, Eudocia Q, Batchelor, Tracy T, Arnaout, Omar, Peruzzi, Pier Paolo, Chiocca, E Antonio, Reardon, David A, Meredith, David, Santagata, Sandro, Beroukhim, Rameen, Bi, Wenya Linda, Ligon, Keith L, Wen, Patrick Y
• Format: Article
• Language: English
• Subjects: Adult; Clinical Investigations; Clinical Trials as Topic; Glioblastoma; Glioblastoma - diagnosis; Glioblastoma - genetics; Glioblastoma - therapy; High-Throughput Nucleotide Sequencing; High-Throughput Nucleotide Sequencing - methods; Humans; Life Sciences; Mutation; Neurons and Cognition; Pathology, Molecular; Retrospective Studies
• ISSN: 1522-8517; 1523-5866; 1523-5866
• DOI: 10.1093/neuonc/noab282

Abstract Background Targeted gene NGS testing is available through many academic institutions and commercial entities and is increasingly incorporated in practice guidelines for glioblastoma (GBM). This single-center retrospective study aimed to evaluate the clinical utility of incorporating NGS results in the management of GBM patients at a clinical trials-focused academic center. Methods We identified 1011 consecutive adult patients with pathologically confirmed GBM (IDHwt or IDHmut) who had somatic tumor sequencing (Oncopanel, ~500 cancer gene panel) at DFCI from 2013–2019. Clinical records of all IDHwt GBM patients were reviewed to capture clinical trial enrollment and off-label targeted therapy use based on NGS results. Results Of the 557 IDHwt GBM patients with sequencing, 182 entered clinical trials at diagnosis (32.7%) and 213 (38.2%) entered after recurrence. Sequencing results for 130 patients (23.3%) were utilized for clinical trial enrollment for either targeted therapy indications (6.9 % upfront and 27.7% at recurrent clinical trials and 3.1% for off-label targeted therapy) or exploratory studies (55.4% upfront and 6.9% recurrent clinical trials). Median overall survival was 20.1 months with no survival difference seen between patients enrolled in clinical trials compared to those who were not, in a posthoc analysis. Conclusions While NGS testing has become essential for improved molecular diagnostics, our study illustrates that targeted gene panels remain underutilized for selecting therapy in GBM-IDHwt. Targeted therapy and clinical trial design remain to be improved to help leverage the potential of NGS in clinical care.