62P Updated overall survival and safety with ripretinib vs sunitinib in patients with advanced gastrointestinal stromal tumor previously treated with imatinib and harboring KIT exon 11 + 17/18 mutations: ctDNA analysis from INTRIGUE
Bibliographic record
Abstract
Ripretinib is a switch-control tyrosine kinase inhibitor approved in the US and EU for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with 3 or more kinase inhibitors, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. In an exploratory analysis of baseline circulating tumor DNA (ctDNA) from the INTRIGUE trial, pts with primary mutations in KIT exon 11 and secondary mutations exclusively in KIT exons 17/18 (KIT exon 11 + 17/18) received clinical benefit from ripretinib but not sunitinib (Heinrich MC, et al. Nat Med. 2024). Here, we present final overall survival (OS) and updated safety in pts with KIT exon 11 + 17/18 mutations from INTRIGUE. INTRIGUE (NCT03673501) is an open-label, phase 3 study of adults with advanced GIST who had disease progression on or intolerance to imatinib. Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Final OS analysis was prespecified to occur with ≥200 and ≥145 events in the all-patient intention-to-treat (ITT) and KIT exon 11 ITT populations, respectively. Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing–based assay. Data cutoff was March 15, 2023. Of 453 pts, ctDNA was analyzed in an exploratory analysis for 362; 52 had mutations exclusively in KIT exon 11 + 17/18 (ripretinib, n = 27; sunitinib, n = 25). Pts with KIT exon 11 + 17/18 mutations had better OS with ripretinib vs sunitinib (median, not reached vs 17.5 months; HR, 0.37; 95% CI, 0.17 to 0.80; nominal P = 0.0091). Fewer of these pts had grade 3/4 drug-related treatment-emergent adverse events and serious adverse events with ripretinib vs sunitinib (33% vs 50% and 3.7% vs 13%, respectively). Median treatment duration in these pts for ripretinib vs sunitinib was 15.6 vs 3.0 months. In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".