TY - JOUR
T1 - Patient-reported outcomes in individuals with advanced gastrointestinal stromal tumor treated with ripretinib in the fourth-line setting
T2 - analysis from the phase 3 INVICTUS trial
AU - Schöffski, Patrick
AU - George, Suzanne
AU - Heinrich, Michael C.
AU - Zalcberg, John R.
AU - Bauer, Sebastian
AU - Gelderblom, Hans
AU - Serrano, César
AU - Jones, Robin L.
AU - Attia, Steven
AU - D’Amato, Gina
AU - Chi, Ping
AU - Reichardt, Peter
AU - Becker, Claus
AU - Shi, Kelvin
AU - Meade, Julie
AU - Ruiz-Soto, Rodrigo
AU - Blay, Jean Yves
AU - von Mehren, Margaret
N1 - Funding Information:
PS has received honoraria from Deciphera, Blueprint, and Boehringer Ingelheim; serves in an advisory/consultancy role for Deciphera, Ellipses Pharma, Blueprint, Transgene, Exelixis, Boehringer Ingelheim, Medscape, Guided Clarity, Adaptimmune, Inteillisphere, and Advanced Medical; his institution has received research funding from CoBioRes NV, Eisai, G1 Therapeutics, Novartis, and PharmaMar; and has received travel, accommodations, expenses from Boehringer Ingelheim, and his institution has received them from MSD and Ipsen. SG serves in an advisory/consultancy role for AstraZeneca, Bayer, Blueprint, Daiichi Sankyo, Deciphera, Eli Lilly, and Exelixis; has a leadership role in Alliance Foundation; receives licensing royalties from Wolters Kluwer Health; is a shareholder/stockholder of Abbott Labs and her institution receives research support from Bayer, Blueprint, Deciphera, Novartis, Daiichi Sankyo, Springworks, Merck, Eisai, and Pfizer. MCH serves in a consultancy role for Novartis, Deciphera, Blueprint, Molecular MD, and Novartis; receives royalties from Novartis; receives research funding from Blueprint and Deciphera; had an equity interest in Molecular MD, and has received travel, accommodations, expenses from Blueprint and Deciphera. JZ serves in an advisory/consultancy role for Merck Serono, Targovax, Merck Sharp & Dohme, Halozyme, Lipotek, Specialised Therapeutics, CEND, Deciphera; owns stock in GW Pharmaceuticals, Aimmune, Vertex, Alnylam, Biomarin, Opthea, Amarin, Concert Pharmaceuticals, Frequency Therapeutics, Global Blood Therapeutics, Gilead, Madrigal Pharmaceuticals, Sangamo Biosciences, Acceleron Pharmaceuticals, Zogenix, Myovant Sciences, Orphazyme, Moderna Therapeutics, and TWST; has received honoraria from Specialised Therapeutics, Merck Serono, Targovax, Halozyme, Gilead Sciences, and Deciphera; and his institution has received research funding from Merck Serono, Bristol-Myers Squibb, AstraZeneca, Pfizer, IQvia, Mylan, Ipsen, Eisai, Medtronic, and MSD Oncology; and has received travel, accommodations, expenses from Merck Serano, AstraZeneca, and Merck Sharp & Dohme. SB serves in an advisory/consultancy role for Blueprint, Bayer, Eli Lilly, Deciphera, Nanobiotix, Daiichi Sankyo, Exelixis, Janssen-Cilag, ADC Therapeutics, Mundipharma, and GSK; has received honoraria from Novartis, Pfizer, Bayer, PharmaMar, and GlaxoSmithKline; has received research funding from Blueprint, and Novartis, and his institution has received research funding from Incyte. HG institution has received research funding from Daiichi Sankyo, Five Prime, Novartis, Deciphera, Eli Lilly, Roche, Eisai, Debio, Boehringer Ingelheim Ltd, Pfizer, Amgen, and TEVA. CS serves in an advisory/consultancy role for Deciphera, Blueprint, and Immunicum; is a member of the speaker’s bureau for Blueprint, and his institution has received research funding from Pfizer, and Karyopharm Therapeutics. RLJ has received honoraria and serves in an advisory role for Adapimmune Therapeutics Plc, Athenex Inc, Bayer, Blueprint, Clinigen Group Plc, Daiichi Sankyo, Deciphera, Eisai, Epizyme, Immunedesign, Eli Lilly, Merck, PharmaMar, UpToDate; and serves in an advisory role for Boehringer Ingelheim Ltd and Tracon Pharma; and has received research funding from MSD. SA has received research funding from Desmoid Tumor Research Foundation; and his institution has received research funding from AB Science, TRACON Pharma, Bayer, Novartis, Eli Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint, Genmab, CBA Pharma, Merck, Philogen, Gradalis, Deciphera, Takeda, Incyte, Springworks, Adaptimmune, Advenchen Laboratories, Barvarian Nordic, BTG, GlaxoSmithKline, and FORMA Therapeutics. GD serves in an advisory/consultancy role for Deciphera. PC serves in an advisory role for Deciphera, Exelixis, Zailab; has received grant funding from Deciphera, Exelixis, Novartis, and Array; and has licensing royalties and owns stock in ORIC. PR serves in an advisory/consultancy role for Clinigen Group, Roche, Bayer, Deciphera, MSD, and Bristol-Myers Squibb; has received honoraria from Novartis, Pfizer, PharmaMar, Eli Lilly, and Amgen; and his institution has received research funding from Novartis. CB is employed by Deciphera. KS is employed by Deciphera, and owns stock in Alnylam, Immunogen, Karyopharm, Deciphera, Spectrum, AstraZeneca and Alberio. JM was employed by Deciphera at the time this analysis was conducted and owns stock in Deciphera. RR-S is employed by Deciphera, and owns stock in Deciphera, and Immunogen. J-YB serves in an advisory/consultancy role and has received honoraria from Novartis, Bayer, Pfizer, Deciphera, PharmaMar, Ignyta, and Roche. MvM serves in an advisory/consultancy role for Deciphera, Blueprint, Exelexis, and GSK; has received travel/accommodation expenses from Deciphera and NCCN; and her institution has received funding from Arog, ASCO, Blueprint, Deciphera, Garadalis, GenMab, Novartis, and Solarius.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Background: Ripretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient-reported outcome (PRO) measures and an exploratory analysis evaluating the impact of alopecia on QoL. Methods: In the INVICTUS trial (NCT03353753), QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L; visual analogue scale). Analysis of covariance (ANCOVA) models compared changes in scores from baseline to treatment cycle 2, day 1 within and between ripretinib and placebo. Within the ripretinib arm, repeated measures models assessed the impact of alopecia on QoL. Results: Patients receiving ripretinib maintained QoL (as assessed by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) from baseline to cycle 2, day 1 whereas QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P < 0.01). The most common treatment-emergent adverse event with ripretinib was alopecia; however, QoL was similarly maintained out to treatment cycle 10, day 1 in patients receiving ripretinib who developed alopecia and those who did not. Conclusion: PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib [6.3 months]), even if the patients developed alopecia. Trial registration: ClinicalTrials.gov Identifier: NCT03353753; first posted: November 27, 2017.
AB - Background: Ripretinib is a novel switch-control kinase inhibitor that inhibits KIT and PDGFRA signaling. In the INVICTUS phase 3 trial, ripretinib increased median progression-free survival and prolonged overall survival vs. placebo in ≥ fourth-line advanced GIST. Here, we report prespecified analysis of quality of life (QoL) as assessed by patient-reported outcome (PRO) measures and an exploratory analysis evaluating the impact of alopecia on QoL. Methods: In the INVICTUS trial (NCT03353753), QoL was assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30; physical function, role function, overall health, and overall QoL) and the EuroQoL 5-Dimension 5-Level (EQ-5D-5 L; visual analogue scale). Analysis of covariance (ANCOVA) models compared changes in scores from baseline to treatment cycle 2, day 1 within and between ripretinib and placebo. Within the ripretinib arm, repeated measures models assessed the impact of alopecia on QoL. Results: Patients receiving ripretinib maintained QoL (as assessed by the EORTC QLQ-C30 and EQ-5D-5 L PRO measures) from baseline to cycle 2, day 1 whereas QoL declined with placebo, resulting in clinically significant differences between treatments (nominal P < 0.01). The most common treatment-emergent adverse event with ripretinib was alopecia; however, QoL was similarly maintained out to treatment cycle 10, day 1 in patients receiving ripretinib who developed alopecia and those who did not. Conclusion: PRO assessments in the INVICTUS trial suggest that patients on ripretinib maintain their QoL out to C2D1, unlike patients receiving placebo. Longitudinal QoL was maintained for patients receiving ripretinib out to cycle 10, day 1 (approximately 8 months; past the point of median progression-free survival with ripretinib [6.3 months]), even if the patients developed alopecia. Trial registration: ClinicalTrials.gov Identifier: NCT03353753; first posted: November 27, 2017.
KW - Alopecia
KW - Gastrointestinal stromal tumors
KW - Patient-reported outcome measures
KW - Quality of life
KW - Ripretinib
UR - http://www.scopus.com/inward/record.url?scp=85144098279&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85144098279&partnerID=8YFLogxK
U2 - 10.1186/s12885-022-10379-9
DO - 10.1186/s12885-022-10379-9
M3 - Article
C2 - 36514034
AN - SCOPUS:85144098279
VL - 22
JO - BMC Cancer
JF - BMC Cancer
SN - 1471-2407
IS - 1
M1 - 1302
ER -