Imatinib of long-term help in some patients with GI stromal tumors

Last Updated: 2017-02-17

By David Douglas

NEW YORK (Reuters Health) - A substantial minority of patients with advanced gastrointestinal stromal tumors (GIST) treated with imatinib mesylate show long-term survival, according to a trial analysis presenting new molecular data.

As Dr. Michael Heinrich explained in an email to Reuters Health, "Prior to 2000, there were no effective medical treatments for advanced GI stromal tumor and patients faced an average life expectancy of 18 months or less. In our study of the long-term treatment results using imatinib . . . we found that approximately 7% of patients were still on front-line therapy at 10 years without any evidence of tumor progression."

In a paper online February 9 in JAMA Oncology, Dr. Heinrich of Oregon Health and Science University in Portland and colleagues note that the original trial conducted in 2000 involved patients with GIST that was not surgically curable. They were treated with imatinib 400 mg once or twice daily.

Updated survival data collected from 2011 to 2015 showed that of 695 eligible patients (mean age, 60.1 years), 189 survived eight years or longer. Of these, 95 had received 400 mg per day and the remaining 94 had received 800 mg per day. Estimated 10-year survival was 23%.

The highest 10-year progression-free and overall survival results were obtained for patients with KIT exon 11-mutant tumors or tumors lacking KIT/PDGFRA mutations.

At the time of study initiation, KIT mutations were the only known pathogenic abnormality associated with GIST. Resequencing studies of 20 cases originally classified as KIT/PDGFRA wild-type GIST revealed that 17 (85%) harbored a pathogenic mutation.

The researchers note that using next-generation sequencing technologies "we now estimate that 97.5% of GIST can be assigned a pathogenic genotype point."

Of 142 long-term survivors, imatinib was the sole therapy administered to 69 (48.6%). Of the remainder, sunitinib malate and sorafenib were the most commonly used additional therapies.

The researchers call for further studies to improve on these results and suggest that "enhanced imaging and biomarker analysis to detect residual GIST cells in patients with long-term response may identify those patients who might benefit from less intense medical therapy."

Commenting on the findings by email, Dr. Joensuu Heikki of Helsinki University, Finland, told Reuters Health, "There are few data available about how long GIST patients with advanced disease may respond to imatinib and other tyrosine kinase inhibitors."

Dr. Heikki, a professor of oncology and radiotherapy, added that the study "confirms that the responses may sometimes be very durable with about a quarter living 10 or more years with metastatic GIST."

"Moreover," he continued, "many of these patients likely had bulky metastases at the time when the metastases were first detected, whereas at present many patients receive adjuvant imatinib, are followed up closely with CT or MRI, and have metastases detected early when they are still small in size. Therefore, even a larger proportion than a quarter of the patients who now have GIST metastases detected may become long-term survivors."

SOURCE: http://bit.ly/2kwG9f7

JAMA Oncol 2017.