Trotabresib (CC-90010) in combination with adjuvant temozolomide or concomitant temozolomide plus radiotherapy in patients with newly diagnosed glioblastoma
| Autor: | Maria Vieito, Matteo Simonelli, Filip de Vos, Victor Moreno, Marjolein Geurts, Elena Lorenzi, Marina Macchini, Martin J van den Bent, Gianluca Del Conte, Maja de Jonge, Maria Cruz Martín-Soberón, Barbara Amoroso, Tania Sanchez-Perez, Marlene Zuraek, Bishoy Hanna, Ida Aronchik, Ellen Filvaroff, Henry Chang, Cristina Mendez, Marina Arias Parro, Xin Wei, Zariana Nikolova, Juan Manuel Sepulveda |
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| Přispěvatelé: | Neurology, Medical Oncology, Institut Català de la Salut, [Vieito M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Simonelli M] Department of Biomedical Sciences, Humanitas University, Milan, Italy. IRCCS Humanitas Research Hospital, Milan, Italy. [de Vos F] Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. [Moreno V] START Madrid-FJD, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. [Geurts M] Erasmus MC Cancer Institute, Rotterdam, the Netherlands. [Lorenzi E] IRCCS Humanitas Research Hospital, Milan, Italy, Vall d'Hebron Barcelona Hospital Campus |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
Glioblastoma multiforme - Tractament
terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Other subheadings::/therapy [Other subheadings] Therapeutics::Radiotherapy [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] General Medicine Neoplasms::Neoplasms by Histologic Type::Neoplasms Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms Neuroepithelial::Glioma::Astrocytoma::Glioblastoma [DISEASES] Glioblastoma multiforme - Radioteràpia Quimioteràpia combinada neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma::astrocitoma::glioblastoma [ENFERMEDADES] terapéutica::radioterapia [TÉCNICAS Y EQUIPOS ANALÍTICOS DIAGNÓSTICOS Y TERAPÉUTICOS] Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL DIAGNOSTIC AND THERAPEUTIC TECHNIQUES AND EQUIPMENT] Temozolomide Pharmacokinetics Trotabresib BET inhibitors Glioblastoma Otros calificadores::/terapia [Otros calificadores] |
| Zdroj: | Neuro-Oncology Advances, 4(1):vdac146. Oxford University Press Scientia |
| ISSN: | 2632-2498 |
| Popis: | Background Standard-of-care treatment for newly diagnosed glioblastoma (ndGBM), consisting of surgery followed by radiotherapy (RT) and temozolomide (TMZ), has improved outcomes compared with RT alone; however, prognosis remains poor. Trotabresib, a novel bromodomain and extraterminal inhibitor, has demonstrated antitumor activity in patients with high-grade gliomas. Methods In this phase Ib, dose-escalation study (NCT04324840), we investigated trotabresib 15, 30, and 45 mg combined with TMZ in the adjuvant setting and trotabresib 15 and 30 mg combined with TMZ+RT in the concomitant setting in patients with ndGBM. Primary endpoints were to determine safety, tolerability, maximum tolerated dose, and/or recommended phase II dose (RP2D) of trotabresib. Secondary endpoints were assessment of preliminary efficacy and pharmacokinetics. Pharmacodynamics were investigated as an exploratory endpoint. Results The adjuvant and concomitant cohorts enrolled 18 and 14 patients, respectively. Trotabresib in combination with TMZ or TMZ+RT was well tolerated; most treatment-related adverse events were mild or moderate. Trotabresib pharmacokinetics and pharmacodynamics in both settings were consistent with previous data for trotabresib monotherapy. The RP2D of trotabresib was selected as 30 mg 4 days on/24 days off in both settings. At last follow-up, 5 (28%) and 6 (43%) patients remain on treatment in the adjuvant and concomitant settings, respectively, with 1 patient in the adjuvant cohort achieving complete response. Conclusions Trotabresib combined with TMZ in the adjuvant setting and with TMZ+RT in the concomitant setting was safe and well tolerated in patients with ndGBM, with encouraging treatment durations. Trotabresib 30 mg was established as the RP2D in both settings. |
| Databáze: | OpenAIRE |
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