Non-Invasive Blood Test Helps Select Treatment for Advanced Gastrointestinal Stromal Tumors

GISTs are part of a group of cancers called sarcomas, which start developing in the tissues that support and connect the body. The targeted therapy drug imatinib is usually the first drug that is used to treat patients with GIST, also termed as first-line treatment. However, patients with advanced GIST whose tumor has not been stopped by imatinib or who are unable to continue taking the drug mostly due to side effects, require different treatment, also called as second-line treatment. Currently, the second-line standard of care treatment for patients with advanced GIST is sunitinib (Sutent), a drug that targets the KIT gene and stops blood vessels from growing in tumors. In cases where sunitinib no longer works for the treatment of GIST, other targeted therapies, including ripretinib (Qinlock), can be used. Now, a new study has found that using a blood-based test can help select the appropriate treatment for patients with advanced GISTs.

The phase III INTRIGUE clinical trial was an international study to test whether ripretinib was more effective for treating advanced GISTs as compared to sunitinib after imatinib can no longer be administered. In the study’s original analysis, ripretinib was found to be as effective as sunitinib as a second-line treatment for GIST. In new, additional analysis from the same clinical trial, researchers at the University Hospital Essen (Essen, Germany) have used a blood test to detect fragments of tumor DNA in the body, called circulating tumor DNA or ctDNA, and then analyzed the ctDNA for specific mutations in the KIT gene. Such a test is also referred to as a liquid biopsy. With the aim of understanding if ripretinib or sunitinib was more effective depending upon the specific type of KIT mutation found in the tumor, the researchers examined the tumor DNA shed into the blood.

For the study, the researchers analyzed 362 tissue samples out of which they detected ctDNA in 280 (77%), and within these samples, found that 213 had KIT mutations (76%). The team found that two most common KIT mutations affected the exons 13 and 14 and exons 17 and 18. An exon is a specific segment of DNA. The researchers found that sunitinib was more effective when there was an exon 13 and 14 mutation on the KIT gene. Sunitinib stopped the tumor growth for 15 months, as against four months taken by ripretinib. Approximately 15% of the subjects in the study saw their tumors shrink with ripretinib, as against 10% with sunitinib. However, ripretinib was more effective in the subjects who had an exon 17 and 18 mutation wherein it stopped the tumor growth for about 14 months, as against two months by sunitinib. About 44% of people who were administered ripretinib saw their tumors shrink, as compared with none for the people who were given sunitinib. Based on these findings, the researchers concluded that for patients with advanced GIST who are no longer being effectively treated with imatinib, a blood test to detect ctDNA may be useful for deciding which second-line targeted treatment can deliver the best results.

“This non-invasive blood test may be a highly meaningful tool to select the most effective drug in patients with GIST who progressed while receiving the first-line treatment with imatinib,” said lead study author Sebastian Bauer, MD, University Hospital Essen. “Our analysis shows that patients with concurrent mutations in KIT exons 11 + 17/18 in the absence of other mutations showed even better overall survival when treated with ripretinib compared to those treated with sunitinib. We plan to validate these data in a new, pivotal phase 3 study. Apart from that, the magnitude of this difference suggests plasma testing to become part of routine care for patients with GIST in the future.”

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University Hospital Essen