Ripretinib Versus Sunitinib in Patients With Advanced Gastrointestinal Stromal Tumor After Treatment With Imatinib (INTRIGUE): A Randomized, Open-Label, Phase III Trial

Author(s): Sebastian Bauer, MD1,2;Robin L. Jones, MD, MBBS3;Jean-Yves Blay, MD, PhD4;Hans Gelderblom, MD, PhD5;Suzanne George, MD6;Patrick Schöffski, MD7;Margaret von Mehren, MD8;John R. Zalcberg, MD, PhD9;Yoon-Koo Kang, MD, PhD10;Albiruni Abdul Razak, MRCP, MBBCh11;Jonathan Trent, MD, PhD12;Steven Attia, DO13;Axel Le Cesne, MD14;Ying Su, MD, PhD15;Julie Meade, MD15;Tao Wang, PhD15;Matthew L. Sherman, MD15;Rodrigo Ruiz-Soto, MD15;and Michael C. Heinrich, MD16,17

Source: DOI: 10.1200/JCO.22.00294 Journal of Clinical Oncology 40, no. 34 (December 01, 2022) 3918-3928.

Dr. Maen Hussein's Thoughts

Second line GIST, no difference in OS or PFS between sunitinib and ripretinib, but ripretinib is more tolerable.

PURPOSE

Sunitinib, a multitargeted tyrosine kinase inhibitor (TKI), is approved for advanced gastrointestinal stromal tumor (GIST) after imatinib failure. Ripretinib is a switch-control TKI approved for advanced GIST after prior treatment with three or more TKIs, including imatinib. We compared efficacy and safety of ripretinib versus sunitinib in patients with advanced GIST who were previously treated with imatinib (INTRIGUE, ClinicalTrials.gov identifier: NCT03673501).

PATIENTS AND METHODS

Random assignment was 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off) and stratified by KIT/platelet-derived growth factor α mutation and imatinib intolerance. The primary end point was progression-free survival (PFS) by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors version 1.1. Secondary end points included objective response rate by independent radiologic review, safety, and patient-reported outcome measures.

RESULTS

Overall, 453 patients were randomly assigned to ripretinib (intention-to-treat [ITT], n = 226; KIT exon 11 ITT, n = 163) or sunitinib (ITT, n = 227; KIT exon 11 ITT, n = 164). Median PFS for ripretinib and sunitinib (KIT exon 11 ITT) was 8.3 and 7.0 months, respectively (hazard ratio, 0.88; 95% CI, 0.66 to 1.16; P = .36); median PFS (ITT) was 8.0 and 8.3 months, respectively (hazard ratio, 1.05; 95% CI, 0.82 to 1.33; nominal P = .72). Neither was statistically significant. Objective response rate was higher for ripretinib versus sunitinib in the KIT exon 11 ITT population (23.9% v 14.6%, nominal P = .03). Ripretinib was associated with a more favorable safety profile, fewer grade 3/4 treatment-emergent adverse events (41.3% v 65.6%, nominal P < .0001), and better scores on patient-reported outcome measures of tolerability.

CONCLUSION

Ripretinib was not superior to sunitinib in terms of PFS. However, meaningful clinical activity, fewer grade 3/4 treatment-emergent adverse events, and improved tolerability were observed with ripretinib.

Author Affiliations

¹Department of Medical Oncology and Sarcoma Center, University Hospital Essen, Essen, Germany ²German Cancer Consortium (DKTK), Partner Site Essen, Germany ³Sarcoma Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom ⁴Centre Léon Bérard, Lyon, France ⁵Leiden University Medical Center, Leiden, the Netherlands ⁶Dana-Farber Cancer Institute, Boston, MA ⁷Department of General Medical Oncology, Leuven Cancer Institute, KU Leuven, University Hospitals Leuven, Leuven, Belgium ⁸Fox Chase Cancer Center, Philadelphia, PA ⁹Monash University School of Public Health and Preventive Medicine and Department of Medical Oncology, Alfred Health, Melbourne, Victoria, Australia ¹⁰Asan Medical Center, University of Ulsan, Seoul, South Korea ¹¹Toronto Sarcoma Program, Princess Margaret Cancer Center, Toronto, ON, Canada ¹²Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, FL ¹³Mayo Clinic, Jacksonville, FL ¹⁴Gustave Roussy, Villejuif, France ¹⁵Deciphera Pharmaceuticals, LLC, Waltham, MA ¹⁶Portland VA Health Care System, Portland, OR ¹⁷OHSU Knight Cancer Institute, Portland, OR

Discontinuation versus continuation of imatinib in patients with advanced gastrointestinal stromal tumours (BFR14): exploratory long-term follow-up of an open-label, multicentre, randomised, phase 3 trial

Imatinib cessation after a good response in met-GIST should not be considered. Based on this study’s results patients should be left on therapy until disease progression or toxicity issues.