Multi-parametric MR-PET imaging predicts pharmacokinetics and clinical response to GDC-0084 in patients with recurrent high-grade glioma

While questions regarding brain penetration and target engagement in experimental therapies are typically answered using early phase surgical studies, an alternative strategy is to use advanced imaging in to quantify downstream physiological changes that are theorized to change as a result of target engagement. The current study demonstrates that a combination of MRI and PET imaging can predict pharmacokinetic parameters and progression-free survival of recurrent malignant gliomas treated with GDC-0084, an oral, brain-penetrant small molecule inhibitor of phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR), likely due to the metabolic consequences of mTOR inhibition and the known role of PI3K in angiogenesis and proliferation. Results from the current study suggest multi-parametric MR-PET imaging targeting biologic processes specific to the drug mechanism of action may be useful for evaluation of treatment efficacy for larger phase II-III studies.