期刊
JOURNAL OF NEURO-ONCOLOGY
卷 149, 期 3, 页码 511-522出版社
SPRINGER
DOI: 10.1007/s11060-020-03641-2
关键词
Ribociclib; Pediatric diffuse intrinsic pontine glioma (DIPG); Pediatric diffuse midline glioma (DMG)
资金
- Novartis Pharmaceuticals
- Cure Starts Now Foundation
- Hope for Caroline Foundation
- Julian Boivin Courage for Cures Foundation
- Abbie's Army
- Michael Mosier Defeat DIPG Foundation
- Reflections of Grace Foundation
- Cure Starts Now Australia
- Brooke Healey Foundation
- Soar With Grace Foundation
- Jeffrey Thomas Hayden Foundation
- Cure Brain Cancer Foundation
- Jones Family Foundation
- Musella Foundation
- Pray, Hope Believe Foundation
- Smiles for Sophie Foundation
- Benny's World
- Love Chloe Foundation
- Aiden's Avengers
- A Cure from Caleb Society
- Operation Grace White Foundation
- Ryan's Hope
- Wayland Villars DIPG Foundation
- American Childhood Cancer Organization
- Juliana Rose Donnelly Trust
- Sheila Jones Friends
- Ellie Kavalieros DIPG Research Fund
- Voices Against Brain Cancer
- DIPG Collaborative
Purpose Cyclin-dependent kinase-retinoblastoma (CDK-RB) pathway is dysregulated in some diffuse intrinsic pontine gliomas (DIPG). We evaluated safety, feasibility, and early efficacy of the CDK4/6-inhibitor ribociclib, administered following radiotherapy in newly-diagnosed DIPG patients. Methods Following radiotherapy, eligible patients received ribociclib in 28-day cycles (350 mg/m(2); 21 days on/7 days off). Feasibility endpoints included tolerability for at least 6 courses, and a less than 2-week delay in restarting therapy after 1 dose reduction. Early efficacy was measured by 1-year and median overall survival (OS). Patient/parent-by-proxy reported outcomes measurement information system (PROMIS) assessments were completed prospectively. Results The study included 10 evaluable patients, 9 DIPG and 1 diffuse midline glioma (DMG)-all 3.7 to 19.8 years of age. The median number of courses was 8 (range 3-14). Three patients required dose reduction for grade-4 neutropenia, and 1 discontinued therapy for hematological toxicity following course 4. The most common grade-3/4 toxicity was myelosuppression. After 2 courses, MRI evaluations in 4 patients revealed increased necrotic volume, associated with new neurological symptoms in 3 patients. The 1-year and median OS for DIPG was 89% and 16.1 months (range 10-30), respectively; the DMG patient died at 6 months post-diagnosis. Five patients donated brain tissue and tumor; 3 were RB+ . Conclusions Ribociclib administered following radiotherapy is feasible in DIPG and DMG. Increased tumor necrosis may represent a treatment effect. These data warrant further prospective volumetric analyses of tumors with necrosis. Feasibility and stabilization findings support further investigation of ribociclib in combination therapies.
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