Nature communications · 2022
Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas.
Клиническое исследование II фазыСтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Brastianos Priscilla K, Kim Albert E, Giobbie-Hurder Anita, Lee Eudocia Quant, Wang Nancy, Eichler April F, Chukwueke Ugonma, Forst Deborah A, Arrillaga-Romany Isabel C, Dietrich Jorg, Corbin Zachary, Moliterno Jennifer, Baehring Joachim, White Michael, Lou Kevin W, Larson Juliana, de Sauvage Magali A, Evancic Kathryn, Mora Joana, Nayyar Naema, Loeffler Jay, Oh Kevin, Shih Helen A, Curry William T, Cahill Daniel P, Barker Fred G, Gerstner Elizabeth R, Santagata Sandro
Аннотация
High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31-0.66) and a median PFS of 7.6 months (90% CI: 3.4-12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.