Imatinib mesylate front-line treatment of advanced or metastatic gastrointestinal stromal tumors (GISTs) leads to significant long-term survival in patients with a specific genetic mutation, according to study published in JAMA Oncology (published online February 9, 2017; doi:10.1001/jamaoncol.2016.6728).
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A phase III study conducted from 2000 to 2008 confirmed imatinib mesylate as an effective treatment and standard of care for patients with advanced and incurable GISTs. Researchers from SWOG, the international cancer research community funded by the National Cancer Institute, investigated the long-term effects in the patients from the original trial in an attempt to present new molecular data regarding treatment outcomes.
Michael Heinrich, MD, professor of medicine and cell and developmental biology, Oregon Health & Science University, and colleagues collected post-study data from 695 patients in the SWOG trial from 2001 to 2015. Researchers used next-generation DNA sequencing on tumor tissues from 20 patients without any mutations of the KIT or platelet-derived growth factor receptor (PDGFRA) genes.
Results of the analysis showed 189 patients survived 8 years or longer as a result of treatment with imatinib, including a 10-year overall survival (OS) estimate of 23% (95% CI, 20%-26%). Among 142 of the long-term survivors, 69 (48.6%) patients were administered imatinib as the sole agent.
Results of the DNA sequencing showed that the highest 10-year progression free survival and OS results were obtained for patients with a KIT exon-11 mutant GIST compared with those who tumors had a KIT exon-9 mutation or without KIT/PDGFRA mutations.
"Our findings show two things," said Dr Heinrich. "One is that [imatinib mesylate] has revolutionized treatment for patients with advanced GISTs. Our findings also highlight the importance of banked biospecimens to drive new scientific findings, and how tumor mutation testing can optimize treatment for cancer patients."
Researchers note that while the results of the study provide guidance for the management of GISTs harboring the most common KIT mutation, it does not offer guidance for the optimal management of other genotypic subtypes. Further research is needed to obtain such information.
