Imatinib confers long-term survival in patients with gastrointestinal stromal tumors

Imatinib treatment conferred a “durable, long-term” OS in nearly a quarter of patients with metastatic gastrointestinal stromal tumors, or GIST, according to findings published in JAMA Oncology.

“Before 2000, GIST was documented to be highly resistant to cytotoxic chemotherapy, with no available effective treatment and a uniformly grim prognosis for patients with metastatic or unresectable disease,” Michael Heinrich, MD, professor of medicine at Oregon Health and Science University in Portland, and colleagues wrote. The researchers noted that the earliest studies on imatinib were carried out in 2001. “Since then, several phase 2 and 3 trials in metastatic disease were conducted, confirming the efficacy of imatinib in metastatic GIST.”

Heinrich and colleagues performed a follow-up study of patients who participated in a randomized clinical trial of imatinib from Dec. 15, 2000, to Sept. 1, 2001. All patients had advanced, unresectable GIST (n = 695). The researchers collected postprotocol data from Aug. 29, 2011, to July 15, 2015, and reanalyzed with more modern sequencing technology 20 cases originally classified as wild-type tumors. Patients had been randomly assigned to either 400 mg once daily or twice daily (800 mg) of imatinib.

Of 695 patients (54.1% men; mean age, 60.1 years) included in the study, 189 survived for at least 8 years — 95 in the 400 mg arm and 94 in the 800 mg arm. Ten-year OS was estimated at 23% (95% CI, 20-26). Among the 142 “long-term survivors,” 69 patients (48.6%) received imatinib as their sole treatment, and 54 (38%) received additional agents.

Seventeen of the 20 resequenced cases originally classified as KIT/PDGFRA wild-type tumors showed a pathogenic mutation of the KIT gene. The highest PFS results overall occurred in patients with KIT exon 11-mutant tumors, which make up between 85% and 88% of GISTs, according to a press release accompanying the study.

“This is a really exciting finding,” Heinrich said in the press release. “Until Gleevec 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 Gleevec.”

“Our findings show two things,” Heinrich said. “One is that Gleevec 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.” – by Andy Polhamus

Disclosure: Heinrich reports consulting or advisory roles with Ariad, Blueprint and Novartis; stock or other ownership with MolecularMD; honoraria from Novartis and Pfizer; research funding from Ariad, Bueprint, Dechipera and Inhibikase; as well as expert testimony and intellectual property with Novartis. Please see the study for a full list of all other researchers’ relevant financial disclosures.