Ctni-78. Pnoc008: a Pilot Trial Testing the Clinical Benefit of Using Molecular Profiling to Determine an Individualized Treatment Plan in Children and Young Adults With Newly Diagnosed High-grade Glioma (excluding Diffuse Intrinsic Pontine Glioma)
Year: 2024
Type: conference-abstract
Abstract: BACKGROUND Despite multiple clinical trials in young patients with newly diagnosed high grade gliomas (HGG), survival remains poor. PNOC008 is a single-arm, multi-center pilot trial, investigating the feasibility, toxicity, and efficacy of a molecularly guided individualized treatment approach following radiotherapy. METHODS Patients aged ≤21 years with newly diagnosed, localized, hemispheric HGG (Stratum A) or non DIPG, diffuse midline glioma (DMG) (Stratum B) were eligible. Comprehensive molecular profiling (targeted gene panel, whole exome, and whole transcriptome sequencing) was performed on primary tumor tissue. The molecular data was reviewed by a dedicated tumor board that recommended an individualized treatment plan combining up to four FDA approved drugs. Patients were followed for toxicity and efficacy. Circulating tumor DNA (ctDNA), imaging, and quality of life (QOL) measures were collected at multiple timepoints. RESULTS Fifty-five HGG patients enrolled between 2018 and 2023 (median age 11 years [range 2-20], n=31 female, n=29 Stratum A), including H3K27-altered (n=17), H3/IDH-wildtype diffuse pediatric-type (n=16), and H3G34-mutant diffuse hemispheric glioma (n=12). In 44 patients that followed the recommended treatment, median overall survival (OS) from time of study enrollment was 26.5 months in Stratum A (lower 95% CI: 18.5) and 23.6 months in Stratum B (lower 95% CI: 16.8), and 30 months in H3G34-mutant patients (n=10, lower 95% CI:24.6) with median follow-up of 34.5 months for all patients (lower 95% CI: 32.2). The treatment recommendations most commonly included alkylator with targeted therapy combinations. The often novel drug combinations were generally well tolerated with grade 3 or 4 treatment-related adverse events being mostly hematologic. Central imaging, ctDNA, and QOL analyses are underway. CONCLUSIONS A personalized treatment approach using comprehensive transcriptomic and genomic analysis is feasible and well tolerated with encouraging survival data in children and young adults with HGG. Further analyses of molecular subgroups and correlatives are ongoing.
Source: Neuro-Oncology
Authors: Lindsay Kilburn, Andrea Franson, Tab Cooney, Cassie Kline, Schuyler Stoller, Alyssa Reddy, Anu Banerjee, Roger Packer, Anne Bendel, Maggie Skrypek, Jane Minturn, Mohamed Abdelbaki, Nicholas Whipple, Priya Chan, John Crawford, Erin Crotty, Angela Waanders, Jennifer Elster, Eric Raabe, Elizabeth George, Soniya Pinto, Nucharin Supakul, Adam Kraya, Michael Prados, Javad Nazarian, David Solomon, Janel Long-Boyle, Annette Molinaro, Sebastian Waszak, Sabine Mueller
Institutions: Children's National, University of Michigan, Dana-Farber Cancer Institute, Children's Hospital of Philadelphia, University of California, San Francisco, Children's Minnesota, Washington University in St. Louis, University of Utah, Children's Hospital of Orange County, Seattle Children's Hospital, Lurie Children's Hospital, Rady Children's Hospital-San Diego, Johns Hopkins University, Johns Hopkins Medicine, St. Jude Children's Research Hospital, Indiana University School of Medicine, University Children's Hospital Zurich, École Polytechnique Fédérale de Lausanne
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4404237791