Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study.

Purpose: In the INTRIGUE trial, ripretinib showed no significant difference versus sunitinib in progression-free survival for patients with advanced gastrointestinal stromal tumour (GIST) previously treated with imatinib. We compared the impact of these treatments on health-related quality of life (HRQoL).
Patients and Methods: Patients were randomised 1:1 to once-daily ripretinib 150 mg or once-daily sunitinib 50 mg (4 weeks on/2 weeks off). Patient-reported outcomes were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer-30 (EORTC QLQ-C30) questionnaire at day (D)1, and D29 of all cycles until treatment discontinuation. Change from baseline was calculated. Time without symptoms or toxicity (TWiST) was estimated as the mean number of days without progression, death, or grade ≥3 treatment-emergent adverse events per patient over 1 year of follow-up.
Results: Questionnaire completion at baseline was 88.1% (199/226) for ripretinib and 87.7% (199/227) for sunitinib and remained high for enrolled patients throughout treatment. Patients receiving sunitinib demonstrated within-cycle variation in self-reported HRQoL, corresponding to the on/off dosing regimen. Patients receiving ripretinib reported better HRQoL at D29 assessments than patients receiving sunitinib on all scales except constipation. HRQoL was similar between treatments at D1 assessments, following 2 weeks without treatment for sunitinib patients. TWiST was greater for ripretinib patients (173 versus 126 days).
Conclusion: Patients receiving ripretinib experienced better HRQoL than patients receiving sunitinib during the dosing period and similar HRQoL to patients who had not received sunitinib for 2 weeks for all QLQ-C30 domains except constipation. Ripretinib may provide clinically meaningful benefit to patients with advanced GIST previously treated with imatinib.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Attia reports institutional research funding from AB Science, Adaptimmune, Advenchen Laboratories, Ayala Pharmaceuticals, Bavarian Nordic, Bayer, Blueprint Medicines, Boehringer Ingelheim, BTG, C4 Therapeutics, CBA Pharma, Deciphera Pharmaceuticals, Eli Lilly & Co, Epizyme, FORMA Therapeutics, Genmab, GlaxoSmithKline, Gradalis, Incyte, InhibRx, Karyopharm Therapeutics, Merck, Monopar Therapeutics, Novartis, Noxopharm, Philogen, PTC Therapeutics, Rain Therapeutics, Salarius Pharmaceuticals, Springworks, Takeda, Theseus Pharmaceuticals, TRACON Pharmaceuticals and Trillium Therapeutics; and personal research funding from the Desmoid Tumour Research Foundation. Dr. Bauer reports honoraria from Novartis; advisory board fees from Roche; consulting fees from Adcendo, Bayer, Blueprint Medicines, Boehringer Ingelheim, Cogent Biosciences, Daiichi Sankyo, Deciphera Pharmaceuticals, Eli Lilly & Co, Exelixis, GlaxoSmithKline, Incyte, Nanobiotix, Novartis and PharmaMar; institutional research funding from Novartis; and travel support from PharmaMar. Dr. Becker has no financial interests to disclose. Dr. Blay reports leadership at Innate Pharma; honoraria from AstraZeneca, Bayer, Bristol Myers Squibb, Deciphera Pharmaceuticals, Ignyta, Merck, PharmaMar and Roche; consulting fees from Bayer, Blueprint Medicines, Deciphera Pharmaceuticals, Karyopharm Therapeutics, PharmaMar and Roche; institutional research funding from AstraZeneca, Bristol Myers Squibb, Bayer, Deciphera Pharmaceuticals, GlaxoSmithKline, Merck, Novartis, OSE Pharma, PharmaMar and Roche; and travel support from Roche. Dr. Boye reports honoraria from Eli Lilly & Co and Novartis; consulting fees from Bayer and GlaxoSmithKline; and institutional research funding from Eli Lillly & Co and Merck. Dr. Chi reports consulting fees from Deciphera Pharmaceuticals, Exelixis, NewBay, Novartis and Zai Lab; institutional research funding from Deciphera Pharmaceuticals and Pfizer/Array; and is a shareholder of Oric Pharma.Dr. Druta reports consulting fees from Eisai and Eli Lilly & Co; and speaker’s bureau fees from Eisai and Eli Lilly & Co. Dr. Gelderblom reports institutional research funding from Daiichi Sankyo, Deciphera Pharmaceuticals, Ipsen and Novartis. Dr. George reports consulting fees from Bayer, Blueprint Medicines, Daiichi Sankyo, Deciphera Pharmaceuticals, Eli Lilly & Co, Kayothera, Immunicum, MORE Health, Research to Practice and UpToDate; institutional research funding from BioAtla, Blueprint Medicines, Daiichi Sankyo, Deciphera, Eisai, IDRX, Merck, Springworks, Theseus Pharmaceuticals and TRACON Pharma; honoraria from CStone Pharmaceuticals; patents, royalties, or other intellectual property with UpToDate; other financial relationships with Research to Practice and WCG/Ayala; and is a shareholder of Abbott Laboratories. Dr. Goldstein reports consulting fees from Deciphera Pharmaceuticals. Dr. Harrow is an employee and shareholder of Deciphera Pharmaceuticals. Dr. Heinrich reports honoraria from Novartis; consulting fees from Blueprint Medicines, Deciphera Pharmaceuticals, Novartis and Theseus Pharmaceuticals; and a patent on the treatment of GIST licensed to Novartis. Dr. Jones reports consulting fees from Adaptimmune, Astex, Athenex, Bayer, Boehringer Ingelheim, Blueprint Medicines, Clinigen, Eisai, Eli Lilly & Co, Epizyme, Daiichi Sankyo, Deciphera Pharmaceuticals, Immunedesign, Immunicum, Karma Oncology, Merck, Mundipharma, PharmaMar, Springworks, SynOx, TRACON Pharmaceuticals and UpToDate. Dr. Kang reports consulting fees from ALX Oncology, Amgen, Novartis, Blueprint Medicines, Bristol Myers Squibb, Daehwa, Macrogenics, Surface Oncology and Zymeworks. Dr. Le Cesne reports honoraria from Bayer, Deciphera Pharmaceuticals, and PharmaMar. Dr. Razak reports consulting fees from Adaptimmune, Bayer, GlaxoSmithKline, Medison, Inhibrx; and research funding from AbbVie, Adaptimmune, Amgen, Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Deciphera Pharmaceuticals, GlaxoSmithKline, Iterion Therapeutics, Karyopharm Therapeutics, Merck, MedImmune, Neoleukin Therapeutics, Pfizer, Roche/Genentech, Rain Therapeutics and Symphogen; and served as expert testimony for Medison. Dr. Reichmann is an employee and shareholder of Deciphera Pharmaceuticals. Dr. Ruiz-Soto is an employee of Deciphera Pharmaceuticals; a shareholder of Deciphera Pharmaceuticals and Immunogen; and is an inventor in three patents with Immunogen and pending patents at Deciphera Pharmaceuticals, the rights for which have been transferred to Immunogen and Deciphera, respectively; Dr. Ruiz-Soto has not received and will not receive royalties from these patents. Dr. Rutkowski reports honoraria from AstraZeneca, Bristol Myers Squibb, Merck, Novartis, Pierre Fabre, and Sanofi. Dr. Sanchez reports honoraria from AstraZeneca, Novartis, Pfizer and Roche; and research funding from Pfizer, Novartis and Roche. Dr. Serrano reports honoraria from Bayer and Blueprint Medicines; institutional research funding from Bayer, Deciphera Pharmaceuticals, Karyopharm Therapeutics and Pfizer; consulting fees from Blueprint Medicines, Cogent Biosciences, Deciphera Pharmaceuticals and Immunicum; and travel support from Bayer, Eli Lilly & Co, Novartis, Pfizer and PharmaMar. Dr. Siontis reports consulting fees from Deciphera Pharmaceuticals and institutional research funding from Advenchen and Deciphera Pharmaceuticals. Dr. Sherman reports employment, leadership, and stock or other ownership interests of Deciphera Pharmaceuticals and Pieris Pharmaceuticals. Dr. Somaiah reports consulting fees from Aadi Biosciences, Boehringer Ingelheim and Epizyme and research funding from Advenchen, Ascentage, AstraZeneca, Cogent, Deciphera Pharmaceuticals, GlaxoSmithKline, and Innovent. Dr. Steeghs reports consulting fees from Boehringer Ingelheim, Cogent Biosciences, Ellipses Pharma and Luszana; institutional research funding from AbbVie, Actuate Therapeutics, Amgen, Array, Ascendis Pharma, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Cantargia, CellCentric, Cogent, Cresecendo Biologics, Cytovation, Deciphera Pharmaceuticals, Eli Lilly & Co, Exelixis, Genentech, GlaxoSmithKline, Incyte, InteRNA, Janssen, Kinnate Biopharma, Luszana, Merck, Merus, Molecular Partners, Navire Pharma, Novartis, Numab Therapeutics, Pfizer, Relay Pharmaceuticals, Revolution Medicine, Roche, Sanofi, Seattle Genetics, Taiho and Takeda. Dr. Trent reports consulting fees from Adcendo, AADI Bioscience, Cogent, Deciphera Pharmaceuticals, Daiichi Sankyo and Foghorn Therapeutics. Dr. von Mehren reports consulting fees from Deciphera Pharmaceuticals, GlaxoSmithKline and Moleculin; institutional research funding from ASCO, Ayala, Deciphera Pharmaceuticals, Genmab, Gradalis, Novartis, Solaris Health, Sumitomo Pharma Oncology and Theseus Pharmaceuticals; and another financial relationship with NCCN. Dr. Zalcberg reports leadership at ICON Group, Lipotek and Praxis; honoraria from Deciphera Pharmaceuticals, Halozyme, Gilead Sciences, Merck Serono, Specialised Therapeutics and Targovax; consulting fees from 1Globe Health Institute, Centre for Emerging and Neglected Diseases (CEND), Deciphera Pharmaceuticals, FivePHusion, Genor BioPharma, Halozyme, Lipotek, Merck, Merck Serono, Novotech, Revolution Medicine, Specialised Therapeutics and Targovax; institutional research funding from AstraZeneca, Bristol Myers Squibb, Eisai, Ipsen, IQVIA, Medtronic, Merck Serono, Mylan and Pfizer; stock or other ownership of Amarin Corporation, Biomarin, Concert Pharmaceuticals, Frequency Therapeutics, Gilead Sciences, Madrigal Pharmaceuticals, Moderna Therapeutics, Novavax, Opthea, Orphazyme, Twist Bioscience, UniQure and Zogenix; and travel support from AstraZeneca, Deciphera Pharmaceuticals, Merck, Merck Serono and Sanofi.
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