ASCO 2022 | INTRIGUE: ripretinib vs. sunitinib in patients with advanced GISTs

Michael C. Heinrich, MD, OHSU Knight Cancer Institute, Portland, OR, provides an overview of the rationale and results of the multicenter, global, randomized, open-label Phase III INTRIGUE (NCT03673501) clinical trial that investigated the efficacy and safety of the KIT and PDGFRA inhibitor tyrosine kinase inhibitor (TKI), ripretinib, versus the multi-targeted TKI, sunitinib, in patients with advanced gastrointestinal stromal tumors (GIST) who had progressed on or were in intolerant to imatinib. Sunitinib is approved is for advanced GIST tumors following failure on imatinib and ripretinib is indicated for the treatment of patients with GIST who had received 3 or more prior lines of treatment, including imatinib. KIT mutations are present in approximately 80% of GIST tumors and PDGFRA mutations in 5-10% of cases. Response to imatinib is not universal amongst patients, and the majority of patients who do respond ultimately develop resistance, commonly arising from secondary mutations in KIT or PDGFRA, thereby generating the rationale for this clinical trial. 453 patients were enrolled and randomized to receive sunitinib or repretinib. The primary endpoint was progression-free survival (PFS) which was not met, whereby a statistically significant difference was not observed. Key secondary endpoints included objective response rate (ORR) and overall-survival (OS). ORR was higher for ripretinib versus sunitinib and, although OS data is still immature, median OS was not reached and. Fewer grade 3-4 treatment-related adverse events was observed in patients treated with ripretinib. This interview took place at the American Society of Clinical Oncology (ASCO) 2022 Annual Meeting in Chicago, IL.