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Imatinib shows strong long-term survival for GIST patients

Nine years ago, SWOG researchers confirmed a new standard of care for patients with incurable gastrointestinal stromal tumours (GIST), who could survive by being treated with imatinib mesylate, the breakthrough drug marketed as Gleevec.

SWOG researchers are back with long-term findings from that study, which estimate that nearly one in four patients treated with imatinib will survive 10 years.

Results are published in JAMA Oncology.

"This is a really exciting finding," said Dr. Michael Heinrich, a SWOG investigator and a professor of medicine and cell and developmental biology at Oregon Health & Science University, where SWOG is based. "Until imatinib arrived on the scene 15 years ago, patients with advanced GISTs faced a life expectancy of 18 months. Now we've learned that some might live a decade or longer. And we've come to understand which class of patients benefit the most from imatinib."

In new study results published in JAMA Oncology, researchers from SWOG, the international cancer research community supported by the National Cancer Institute, report a follow-up of patients originally enrolled in S0033, a SWOG-led trial supported by other groups in the NCI's National Clinical Trials Network (NCTN).

This was a Phase III study that began in 2000.

Initial results published in 2008 confirmed imatinib as an effective treatment for advanced GIST patients, and recommended that therapy start with a 400 mg daily dose.

The SWOG team decided to collect post-study data on S0033 patients, and from 2011 to 2015 gathered information.

As part of their research, the team used next-generation DNA sequencing on some tumour tissue samples taken for S0033, which had been deposited in a biospecimen bank.

The team reanalyzed tissue from 20 patients originally classified as having a wild-type tumour - one without any mutations of KIT, a gene implicated in 85 to 88 percent of all GISTs.

Analysis showed that of the 695 eligible patients originally enrolled in S0033, 189 survived eight years or longer, with a 10-year estimate of overall survival of 23 percent, or nearly one in four patients.

DNA sequencing also showed that survival rates were significantly higher for patients with a KIT exon-11 mutant GIST, when compared with patients whose tumour had a KIT exon-9 mutation or with no KIT mutations or mutations in the platelet-derived growth factor receptor gene, or PDGFRA.

"Our findings show two things," Heinrich said. "One is that imatinib has revolutionised treatment for patients with advanced GISTs. Our findings also highlight the importance of banked biospecimens to drive new scientific findings, and how tumour mutation testing can optimise treatment for cancer patients."

GISTs are different from more common types of gastrointestinal tumours because of the type of tissue in which they start.

GISTs belong to a group of cancers called soft-tissue sarcomas.

Soft-tissue sarcomas develop in the tissues that support and connect the body, including muscles, nerves, tendons, and joints.

GIST is a rare cancer, with about 6,000 new cases diagnosed in the United States each year.

Researchers at Oregon Health & Science University have pioneered the treatment of GISTs.

Dr. Brian Druker, director of the OHSU Knight Cancer Institute, conducted the most influential work in the development of imatinib and OHSU researchers have been part of major discoveries in the use of the drug to treat GISTs, as well as chronic myeloid leukaemia (CML) and acute lymphoblastic leukaemia (ALL).

Source: SWOG

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Cancer Intelligence