Targeted Therapy for Treating Advanced Gastrointestinal Stromal Tumors (GISTs): The ASCO Plenary Series

ASCO ® Plenary Series
January 24, 2022
Brielle Gregory Collins, ASCO staff

The pace of progress in cancer research keeps getting faster and faster. However, the results of this research can take time to reach the medical community. The ASCO Plenary Series is a program developed by the American Society of Clinical Oncology (ASCO) to help speed the delivery of high-impact cancer research. In this series, cancer care providers gather online to learn about new, carefully selected research and discuss the study results with their colleagues.

The January 2022 session in the ASCO Plenary Series features a study on the treatment of advanced gastrointestinal stromal tumors (GISTs).

  • Ripretinib compared to sunitinib in treating advanced GISTs

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Ripretinib compared to sunitinib in treating advanced GISTs

Who does this study affect: People with advanced GIST who cannot continue taking imatinib (Gleevec).

What did this study find: A GIST is a specific type of tumor that forms in the gastrointestinal tract, which is the body’s system for digesting food. GISTs are part of a group of cancers called sarcomas, which begin in tissues that support and connect the body. There were an estimated 4,000 to 6,000 people diagnosed with a GIST in the United States in 2021.

The targeted therapy drug imatinib is often the first drug used to treat people with GIST, also called first-line treatment. But for people with advanced GIST whose tumor has not been stopped by imatinib or who cannot continue taking the drug, often because of side effects, different treatment is needed. When this is the case, it is called second-line treatment. The current second-line standard of care treatment for advanced GIST is sunitinib (Sutent), which is a drug that targets the KIT gene and stops blood vessel growth in tumors. If sunitinib no longer works to treat the GIST, then other targeted therapies, including ripretinib (Qinlock), may be used.

The phase III INTRIGUE clinical trial was an international study designed to test whether ripretinib was more effective at treating advanced GISTs than sunitinib after imatinib could no longer be used.

This study included 453 people with an advanced GIST who needed second-line treatment. The participants were randomly assigned to receive treatment with either ripretinib (226 people) or sunitinib (227 people). About 80% of GISTs have a mutation in the KIT gene. One of the most common KIT mutations in GISTs is called KIT exon 11. Of all participants, 327 had a KIT exon 11 mutation. Because both sunitinib and ripretinib target the KIT gene, the researchers also evenly divided participants with an exon 11 mutation among the 2 study groups.  

The participants in this study came from 22 different countries, and 66.2% were white, 12.8% were Asian, and 6.2% were Black. There were 8.6% of participants who identified as having Hispanic or Latino ethnicity. The majority of the participants were male (62% of participants), and the median age of the participants was 60, though they ranged in age from 18 to 88. The median is the midpoint, meaning half of the participants were younger than 60 and the other half were older than 60.

In this study, the researchers evaluated both treatments using progression-free survival (PFS), which is the length of time that the treatment stops the tumor from growing or spreading. They found no statistical difference in PFS between ripretinib (median of 8.3 months in patients with a KIT mutation and median of 8 months in all patients) and sunitinib (median of 7 months in patients with a KIT mutation and median of 8.3 months in all patients). The overall response rate (ORR), which is the percentage of participants whose tumors shrunk from the treatment, was higher in those who received ripretinib versus sunitinib in both patients with a KIT mutation and the overall participant population. In patients with a KIT mutation, ripretinib had an ORR of 23.9% compared to 14.6% for sunitinib, and in the overall participant population, ripretinib had an ORR of 21.7% compared to 17.6% for sunitinib. However, the difference in ORR between the treatment groups was not statistically significant.

Those who received ripretinib experienced fewer serious side effects than those receiving sunitinib, with 41.3% of those receiving ripretinib experiencing a serious side effect versus 65.6% of those receiving sunitinib. Among those side effects were high blood pressure (8.5% of participants receiving ripretinib vs. 26.7% of participants receiving sunitinib); a skin reaction called hand-foot syndrome (1.3% of those receiving ripretinib vs. 10% of those receiving sunitinib); decreased counts of neutrophils, which is a type of white blood cell (0% of those receiving ripretinib vs. 7.2% of those receiving sunitinib); and neutropenia, which is a low level of neutrophils (0% of those receiving ripretinib vs. 6.3% of those receiving sunitinib).

What does this mean for patients: While ripretinib is not better than sunitinib in controlling advanced GIST after imatinib, it does appear to offer similar effectiveness to sunitinib and cause fewer serious side effects than sunitinib.

Read this abstract and authors’ disclosures on ASCO.org.

“Even though the INTRIGUE study did not meet its primary endpoint of improved PFS, ripretinib and sunitinib efficacy appeared comparable. Although ripretinib was not superior to sunitinib as a second-line treatment for GIST, ripretinib has remarkable activity as a fourth-line or later agent and remains the only FDA-approved agent in this setting.”

—   lead study author Michael C. Heinrich, MD, FACP
Oregon Health & Science University
Portland, Oregon

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