Abstract 997: Impact of a personalized medicine research program (PMRP), using targeted tumor profiling and a cloud based clinical trials matching platform, on clinical decision-making
Authors: Brown Thomas D. , Tittel Paul D. , Gold Philip J. , Drescher Charles W. , Pagel John M. , Beatty J D. , Grevstad Patra , Iriarte Desiree , Alexander Shlece , Brindle Madeleine , Liu Xiaoyu , O'connor Donielle , Tameishi Mariko , Xu Danbin , Berry Anna B. 
Published: July 2017

Background: Cancer care is evolving to a model of precision medicine where genomic changes in a patient's tumor are used to inform individualized management (mgmt). The optimal approach and impact of tumor profiling on cancer care remain important research questions. We report the impact on clinical decision-making by results from a PMRP in a research practice.

Methods: A custom designed next generation sequencing (NGS) 68 gene alteration (GA) panel, covering clinically relevant genes and regions was developed in 2014. The NGS results were used to: 1) prioritize standard therapies; 2) match patients (pts) with clinical trials (CT); and 3) serve as a data mining resource. NGS testing was offered early in the course of mgmt. An Institutional Review Board approved prospective registration protocol (PMRP) was activated in 2014, with the objective of establishing a centralized longitudinal, molecular phenotypic, and research data repository. Primary endpoints include proportion of pts where NGS impacted mgmt, to include enrollment onto CT. A cloud-based informatics platform was developed to: manage PMRP; facilitate CT matching; perform quality assurance/quality improvement; pursue research initiatives.

Results: As of 11/15/2016, 869 pts gave informed consent, with 844 pts enrolled. The top primary sites included: breast (115); colorectal (111); central nervous system (103); lung (91); ovary (49); hematologic malignancies (46); pancreas (37); uterus (28); esophagus (25); skin (21). Of solid tumor pts with documented clinical stage, 130 (40%) pts had early stage cancer (I, II and III), and 193 (60%) pts had advanced stage (IV) cancer. NGS results: 739 (88%) pts with GA found; 27 (3%) pts without GA. Of pts with GA, 178 (24%) pts had actionable (on-label drugs) GA and 476 (64%) pts had applicable (off-label or CT) GA, for a total of 546 (74%) pts with actionable and/or applicable GA. The top actionable GA were: KRAS (125); PIK3CA (17); BRAF (13); EGFR (12); NRAS (11); AKT1 (3); TET2 (2); ERBB2 (2); HRAS (2). The top applicable GA, included: TP53 (225); TPMT (78); TYMS (78); PIK3CA (77); APC (56); PTEN (52); IDH1 (34); CDNK2A (22); CTNNB1 (18); TET2 (16). Care mgmt impact was reported by physicians for 508 pts with actionable/applicable GA. Physicians reported mgmt impact, at time of reporting, for 105 (21%) pts, to include: new treatment (Tx) in 30 (6%) pts; no Tx given in 18 (4%) pts; Tx changed in 12 (2%) pts; Tx stopped in 1 (&lt;1%) pt; 6 (1%) pts enrolled onto CT. In 403 (79%) pts, physicians reported no mgmt impact, to include: insufficient evidence in 294 (58%) pts; drugs/CT access in 91 (18%) pts; refused Tx in 17 (3%) pts.

Conclusions: NGS profiling of tumors with this 68 GA panel has an impact on clinical decision- making in a minority, though substantial number, of pts. Impact on CT participation remains modest. Access to drugs and CT remains an important barrier.

Citation Format: Thomas D. Brown, Paul D. Tittel, Philip J. Gold, Charles W. Drescher, John M. Pagel, J D. Beatty, Patra Grevstad, Desiree Iriarte, Shlece Alexander, Madeleine Brindle, Xiaoyu Liu, Donielle O'connor, Mariko Tameishi, Danbin Xu, Anna B. Berry. Impact of a personalized medicine research program (PMRP), using targeted tumor profiling and a cloud based clinical trials matching platform, on clinical decision-making [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 997. doi:10.1158/1538-7445.AM2017-997