A. J. Bartholomew1, H. Dohnalek1, P. Prins2, H. S. Quadri3, L. B. Johnson3, N. G. Haddad4, J. L. Marshall2,5, W. B. Al-Refaie2,3,6,7 1Georgetown University Medical Center,School Of Medicine,Washington, DC, USA 2Georgetown University Medical Center,Lombardi Comprehensive Cancer Center, Ruesch Center For The Cure Of Gastrointestinal Cancers,Washington, DC, USA 3Georgetown University Medical Center,Surgery,Washington, DC, USA 4Georgetown University Medical Center,Gastroenterology,Washington, DC, USA 5Georgetown University Medical Center,Hematology/Oncology,Washington, DC, USA 6MedStar-Georgetown Surgical Outcomes Research Center,Washington, DC, USA 7MedStar Health Research Institute,Hyattsville, MD, USA
Introduction: Tyrosine kinase inhibitors (TKI) have become the guideline-recommended therapy for high-risk resected, recurrent, and metastatic gastrointestinal stromal tumors (GIST). Exon mutational analysis (EMA) is used to inform pre-therapy response to TKI and may predict overall prognosis. Despite these benefits, EMA remains underused, and its impact on TKI therapy decision-making remains unexplored. We sought to better characterize the use of EMA in GIST patients receiving TKI and to quantify the subsequent impact on treatment at a comprehensive cancer center.
Methods: A retrospective cohort was established from 104 patients who received treatment for pathologically confirmed, c-KIT-positive and -negative GIST from 2006 to Jan 2017. Variables collected included patient, tumor, and treatment characteristics. According to current National Comprehensive Cancer Network (NCCN) guidelines, EMA should be considered for all patients undergoing TKI therapy to identify genotypes that will, or will not, respond to treatment. We first tracked guideline-considered EMA use in GIST patients who received TKI over time. We then identified how the return of EMA results informed treatment decision-making across the study period.
Results: Among the 104 GIST patients, 54 (52%) of patients received adjuvant or neoadjuvant TKI. Of these 54 patients, only 22 (41%) received EMA, as considered by NCCN guidelines. The use of EMA varied during our study course (Figure 1). Genotypes identified from EMA included 50% of patients with a mutation in KIT exon 11, 5% with KIT exon 9, 9% with PDGFRA exon 18, and 36% with wildtype GIST. Informed by these EMAs, TKI treatment decisions included 59% who continued on their original TKI regimen, 32% who switched to an alternative TKI treatment, and 9% who discontinued TKI treatment based on primary resistance.
Conclusion: Less than half of patients receiving TKI therapy for GIST received EMA at a comprehensive cancer center. Despite this low uptake, when it was performed, EMA resulted in an alternative treatment decision in 41% of patients. Future interventions are needed to identify and mitigate barriers responsible for underuse of EMA prior to initiating TKI therapy for GIST.
