CTNI-61. CLINICAL EFFICACY AND PREDICTIVE BIOMARKERS OF ONC201 IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA
| العنوان: | CTNI-61. CLINICAL EFFICACY AND PREDICTIVE BIOMARKERS OF ONC201 IN H3K27M-MUTANT DIFFUSE MIDLINE GLIOMA |
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| المؤلفون: | Abed Rahman Kawakibi, Rohinton Tarapore, Sharon Gardner, Andrew Chi, Sylvia Kurz, Patrick Y Wen, Isabel Arrillaga-Romany, Tracy Batchelor, Nicholas Butowski, Ashley Sumrall, Nicole Shonka, Rebecca Harrison, John DeGroot, Minesh Mehta, Yazmin Odia, Matthew Hall, Doured Daghistani, Timothy Cloughesy, Benjamin Ellingson, Michelle Kim, Yoshie Umemura, Hugh Garton, Andrea Franson, Jonathan Schwartz, Sunjong Li, Rodrigo Cartaxo, Karthik Ravi, Evan Cantor, Jessica Cummings, Alyssa Paul, Dustin Walling, Matthew Dun, Jason Cain, Jiang Li, Mariella Filbin, Lili Zhao, Chandan Kumar-Sinha, Rajen Mody, Arul Chinnaiyan, Ryo Kurokawa, Drew Pratt, Sriram Venneti, Jacques Grill, Cassie Kline, Sabine Mueller, Adam C Resnick, Javad Nazarian, Sebastian Waszak, Joshua E Allen, Carl Koschmann |
| المصدر: | Neuro-Oncology. 24:vii86-vii87 |
| بيانات النشر: | Oxford University Press (OUP), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Cancer Research, Oncology, Neurology (clinical) |
| الوصف: | Patients with H3K27M-mutated diffuse midline glioma (DMG) have no proven effective therapies beyond radiation. ONC201, a DRD2 antagonist and mitochondrial ClpP agonist, has shown promise in this population. Clinical and genetic variables associated with ONC201 response in H3K27M-mutant DMG continue to be investigated. A combined clinical and genetic study evaluated patients with H3K27M-DMG treated with single-agent ONC201 at the established phase 2 dose. Clinical outcomes of patients treated on two recently completed multi-site clinical studies (NCT03416530 and NCT03134131, n = 75) were compared with historical control data from patients with confirmed H3K27M-DMG (n = 391 total, n = 119 recurrent). Patients treated with ONC201 monotherapy following initial radiation, but prior to recurrence, demonstrated a median overall survival (OS) of 25.6 months from diagnosis and recurrent patients demonstrated a median OS of 16.2 months from recurrence, both of these more than doubling historical outcomes. Using a Cox model to correct for age, gender and tumor location, OS of ONC201-treated patients with H3K27M-mutant tumors remained significantly better than non-ONC201-treated historical controls (p = 0.0001). A survival and radiographic analysis based on tumor location, revealed stronger responses in thalamic patients. In patients with thalamic tumors treated after initial radiation (n = 16), median OS was not reached with median follow up of 22.1 months (historical control median OS of 12.5 months, n = 83, p = 0.0001). Significant correlations were found between baseline cerebral blood flow (CBF) on perfusion imaging and OS (Pearson’s r = 0.75, p = 0.003) and between nrCBF and PFS (r = 0.77, p = 0.002). Baseline tumor sequencing from treated patients (n = 20) demonstrates EGFR mutation (n = 3) and high EGFR expression as a marker of resistance and improved response in tumors with MAPK-pathway alterations (n = 5). In conclusion, ONC201 demonstrates unprecedented clinical and radiographic efficacy in H3K27M-mutant DMG with outcomes enriched in patients with thalamic tumors, treatment prior to recurrence, MAPK-pathway alterations, and patients with relatively high CBF. |
| تدمد: | 1523-5866 1522-8517 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::036ba8c3615a5a91df3fc469db7f43ac https://doi.org/10.1093/neuonc/noac209.326 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........036ba8c3615a5a91df3fc469db7f43ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15235866 15228517 |
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