Bryan P. Schneider, MD

2011-2012 BCRF Project:
Neuropathy, one of the most common toxicities associated with taxane therapy (e.g. paclitaxel, docetaxel), may be severe, function-limiting, and sometimes irreversible. Established predictors for increased risk include advanced age, diabetes, and type/dose/schedule of taxane. No established biomarkers have been identified to predict patients who are at greatest risk. Dr. Schneider proposes to build on several relevant multi-institutional clinical trials which have been performed through the Eastern Cooperative Oncology Group (ECOG). He plans to validate findings from the E1199 clinical trial, which was a pivotal phase III trial that directed the optimal schedule/type of taxane to be used in the adjuvant setting for breast cancer. In that trial, weekly paclitaxel was found to have superior survival when compared with the control arm of every three week paclitaxel. Unfortunately, this drug/schedule had the highest risk of neuropathy as well. Dr. Schneider will now assess the top 512 candidate SNPs (from E5103) with neuropathy in E1199. In addition, he hopes to determine the threshold of discrimination necessary for a predictive genomic biomarker to be clinically relevant. He will formally assess what incremental increase in toxicity is necessary for a patient to alter a therapeutic decision. In summary, he plans to validate the findings in E1199 and create a clinically relevant genetic signature to best counsel patients on the individualized efficacy: toxicity ratio for the taxanes.

Mid-year Progress: Working with fellow BCRF grantee, Dr. George Sledge, Jr., Dr. Schneider continue his work aimed at understanding the role of germline genetic variation as predictors for both efficacy and toxicity for the anti-VEGF monoclonal antibody, bevacizumab. Their current work plans to expand this signature by using top associations from the clinical trial E5103 (a 5000 patient phase III breast cancer trial for bevacizumab in the adjuvant setting) to be validated in E2100 (a first line metastatic trial for bevacizumab). They performed a genome wide association study (GWAS) for the first 2204 patients in E5103 and found multiple provocative associations with the most common toxicity specific to bevacizumab, hypertension. They have more recently performed another genome wide assessment on an addition 1,150 patients from E5103 in an attempt to replicate their initial findings. With BCRF funding, Dr. Schneider and colleagues plan to also validate this signature in the metastatic setting in the E2100 clinical trial. They will soon be selecting their final "top" SNPs to be genotyped in an open-array platform in that trial; this work is currently ongoing. From the GWAS of E5103, these researchers were also able to explore the association of other toxicities with germline genetic variation.

Bio:
Dr. Schneider is an Associate Director of the Indiana Institute for Personalized Medicine and an Assistant Professor of Medicine at the Indiana University Melvin and Bren Simon Cancer Center. He holds appointments in the Divisions of Hematology/Oncology and Clinical Pharmacology in the Department of Medicine with a secondary appointment in the Department of Medical and Molecular Genetics. Dr. Schneider completed his Medical School, Internal Medicine Residency and Hematology/Oncology Fellowship at Indiana University.

Dr. Schneider devotes his clinical time caring for breast cancer patients as a medical oncologist and has a special interest in novel therapeutic agents. He is the model example of a translational scientist, as his laboratory work is both an extension of and complementary to his clinical interesst. His laboratory focus is on pharmacogenetics of breast cancer therapeutics. His biomarker work to date has opened the door for the potential enrichment of patient selection for bevacizumab (Avastin®).

Based on his early work, Dr. Schneider has designed correlative trials in collaborations with multiple groups to better guide proper patient selection for these agents. He is extensively published in the area of therapeutic individualization (i.e. "finding the right drug for each patient.") He is a recipient of the Komen Promise Award and a member of the Komen Scientific Advisory Council. Dr. Schneider is the Chair of the Educational Symposium for the Developmental Therapeutics Committee, the Vice-Chair of the Pharmacogenetics Committee, and a member of the Breast Cancer Committee for the Eastern Cooperative Oncology Group (ECOG). He is also a member of the Consortium on Breast Cancer Pharmacogenetics (CoBRA) and the Pharmacogenetics Research Network (PGRN).