Press Release: Kwatra Lab publishes its findings on osimertinib’s efficacy against EGFRvIII+ glioblastoma in preclinical models.

On June 2, 2020, Dr. Kwatra and his collaborators published their findings on osimertinib’s efficacy against EGFRvIII+ glioblastoma in the journal Oncotarget.
The study began in 2015 when Dr. Kwatra and his co-PI, Dr. Glenn Lesser at Wake Forest University, received a grant from NIH/NCATS and AstraZeneca. At the time, AstraZeneca was developing osimertinib, then called AZD9291, for lung cancer patients. Osimertinib was approved by the FDA for lung cancer patients in 2015. Preliminary findings of our follow-up study were published at the 2017 Society of Neuro-Oncology meeting.
This new study shows that EGFRvIII+ GBMs are heterogeneous, and osimertinib may be effective in some patients with EGFRvIII+ GBM tumors. Future studies are planned to identify the molecular characteristics of EGFRvIII+ tumors that make the tumor most sensitive to osimertinib. Once this information is obtained, osimertinib will be tested in a refined, specific group of EGFRvIII+ GBM patients.
Osimertinib, as Dr. Kwatra detailed in his 2017 review, is the most promising EGFR blocker tested so far in GBM patients because it penetrates the brain well and potently inhibits the growth of EGFRvIII+ GBMs with higher EGFRvIII tyrosine kinase activity. Failure of previous drugs targeting EGFR (such as afatinib, erlotinib, gefitinib, and lapatinib) can be explained by 1) the fact that they do not penetrate the brain well and 2) the studies of past EGFR inhibitors were done on a broad spectrum of patients without molecularly profiling their tumors. However, our understanding of GBM tumor heterogeneity has increased considerably, and now we can study these drugs correctly.
Thus, we are confident that osimertinib will show an effect in a subset of molecularly-defined patients. Dr. Kwatra and his collaborators at Cornell-Weil, Johns Hopkins, National Cancer Institute, and University of Alabama at Birmingham continue to work on the personalized development of osimertinib to ensure the promising drug receives FDA approval for a subset of GBM patients with specific molecular characteristics. Furthermore, preliminary studies on GBM patients conducted by Dr. Lesser show benefits of osimertinib therapy. Please read our new publication here.

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