A Phase I/II Study of Ribociclib Following Radiation Therapy in Children with Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

Authors: Mariko DeWire et al. (2020)

Link: https://link.springer.com/article/10.1007/s11060-020-03641-2
 

Background Information:

Diffuse intrinsic pontine glioma (DIPG) is a rare but devastating brainstem tumor found almost exclusively in children. It grows within a critical brain area controlling functions like breathing and movement, making surgery nearly impossible. Even with standard treatment—radiation therapy—children typically live less than a year. Researchers have discovered that many DIPGs have mutations that disrupt the CDK4/6–retinoblastoma (RB) cell-cycle pathway, which drives tumor growth. Ribociclib is a targeted drug designed to block CDK4/6 and has shown promise in other cancers by slowing cell division.

Purpose of the Study:

This trial aimed to determine whether ribociclib, given after standard radiation therapy, is safe, tolerable, and potentially beneficial in children newly diagnosed with DIPG or similar diffuse midline gliomas. The researchers wanted to see if children could complete at least six treatment cycles without serious side effects and whether early data suggested that this approach might help extend survival beyond what is typical for DIPG.

Methods and Data Analysis:

The study enrolled ten children aged 3.7 to 19.8 years who had completed radiation therapy for DIPG (nine patients) or diffuse midline glioma (one patient). Starting four to six weeks after radiation, participants took ribociclib in 28-day cycles (21 days on, 7 days off) until side effects or disease progression occurred. Safety was assessed by tracking blood counts and other labs. MRI scans were done every two cycles to check tumor response. Parents completed standardized health-related quality-of-life surveys (PROMIS), and survival outcomes—like one‑year survival and median overall survival—were recorded.

Key Findings and Conclusions:

Ribociclib was generally safe and feasible: eight children stayed on at least six cycles, although three needed dose reductions for low white blood cell counts and one stopped due to blood toxicity. MRI scans in four children showed increased tumor necrosis after two cycles—meaning parts of the tumor may have died—which was sometimes accompanied by new neurological symptoms. Importantly, nine DIPG patients achieved a one-year survival of 89%, and the median overall survival was 16.1 months—substantially longer than the typical ~9 months seen with radiation alone. The one diffuse midline glioma patient survived six months.

Applications & Limitations:

This trial indicates that it is possible to safely add ribociclib to standard radiation in children with DIPG and that the approach might extend survival. The increased tumor necrosis seen on scans hints at biological activity, but it's too early to conclude effectiveness. Limitations include the very small sample size, lack of a control group, and early-phase design focused on safety rather than definitive proof of benefit. Still, the results provide justification for larger, controlled trials—possibly combining ribociclib with other targeted agents—to improve outcomes in this nearly always fatal childhood cancer.