Thus far, bevacizumab has been the only agent approved by the Food and Drug Administration for use in the setting of recurrent GBM. Studies are currently underway to assess the up-front efficacy of using bevacizumab with radiotherapy and TMZ. Given the dismal prognosis for this patient population, novel agents are needed not only to augment up-front therapy to prevent recurrence but also to provide further treatment options in the recurrent setting.
Ms. Gilbert and colleagues conducted an eloquent study using a novel GSI to assess influence on neurosphere replication in the pre-, adjunct, and post-TMZ treatment periods. The remarkable in vitro and in vivo data suggest that GSI and TMZ act together to halt neurosphere replication, and that administering a GSI after TMZ may have the maximum impact in affecting neurosphere repopulation. These data suggest that GSIs may indeed have an impact on glioblastoma recurrence and time to progression.
As the authors point out, future studies to assess the total impact of the GSI in the GBM population will need to incorporate irradiation in addition to TMZ to reflect a more accurate sense of the full effect and toxicity of the GSI. Toxicity was measured in this study by rodent weight; according to the data provided, it seemed well tolerated with TMZ. The authors suggest that GSIs may also improve the impact of irradiation, which may further reduce treatment toxicity. This study certainly provides a springboard for considering future directions in the use of GSIs and may indeed provide further treatment options for this patient population, in whom options are greatly needed.
ALYX B. PORTER, M.D., is a neuro-oncologist at the Mayo Clinic in Arizona. She has no relevant disclosures.