Successful Findings from ctDNA Analysis for Patients with Advanced Gastrointestinal Stromal Tumor (GIST)
An exploratory next generation sequencing (NGS) analysis of circulating tumor DNA (ctDNA) in patients with advanced GIST participating in the randomized phase 3 INTRIGUE trial that compared ripretinib with sunitinib in patients with advanced GISTs highlights the clinical value of molecular testing for GIST patients.
Data from this study unveiled positive outcomes for a specific subgroup of patients. Out of 453 patients in the overall intent-to-treat population (ITT), 362 patients with adequate samples had baseline ctDNA analyzed. ctDNA was detected in 280 samples and KIT mutations were detected in 213 patients. Of those 213 patients, 52 patients had KIT exon 11 plus 17 and/or 18 mutations and 41 had KIT exon 11 plus 13 and/or 14 mutations.
Researchers then analyzed and compared progression-free survival (PFS) and overall survival (OS) between patients taking ripretinib or sunitinib. They found patients with KIT exon 11 plus 17 and/or 18 mutations that took ripretinib demonstrated superior outcomes when compared were patient that took sunitinib. On the other hand, patients with KIT exon 11 plus 13 and/or 14 mutations showed better outcomes when treated with sunitinib versus ripretinib.
Summary of INTRIGUE Efficacy Results of ctDNA Analysis for Patients
Patients with KIT exon 11 plus 17 and/or 18 mutations demonstrated a superior PFS (14.2 vs 1 months), median overall survival (OS; not estimable vs. 17.5 months), and objective response rate (ORR; 44.4% vs 0%) when they received ripretinib as a second-line treatment compared with sunitinib. On the other hand, patients with KIT exon 11 plus 13 and/or 14 mutations showed better median PFS (15.0 vs 4.0 months), median OS (not estimable vs 24.5 months), and ORR (15.0% vs 9.5%) when treated with sunitinib versus ripretinib.
These new data were presented by Dr. Sebastian Bauer of the West German Cancer Centre in Essen, Germany and Dr. Breelyn A. Wilky of the University of Colorado Anschutz Medical Campus in Aurora, Colorado during the 2023 January ASCO Plenary Series.
This is the first-time blood-based biomarkers have demonstrated a correlation with a response to second-line treatment in patients with imatinib-resistant GISTs. These findings highlight the clinical value of molecular testing in precision medicine. This informs us that each treatment therapy is tailored to each individual patient to ensure a better outcome and treatment response for GIST patients.
Due to these findings, Deciphera Pharmaceuticals announced that they will initiate a Phase 3 clinical trial INSIGHT. This purpose of this clinical trial is to study ripretinib versus sunitinib in second-line GIST patients with mutations in KIT exon 11 and 17/18 only. Approximately 54 patients will be randomized. Deciphera expects to begin the INSIGHT study in the second half of 2023. A patient-friendly version of the INSIGHT protocol summary will be shared with patient community soon.
We are very excited and eager to see that testing and treatment practices for GIST are moving towards a precision medicine path. This is a successful finding for GIST, and we will continue to encourage our GIST community to raise awareness on mutational testing to ensure the best possible care for all patients taking treatments.
If you have any questions or comments about this, please feel free to contact Denisse Evans at devans@liferaftgroup.org
