Browsing by Author "Razak, Albiruni Abdul"

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    Patient-reported outcomes and tolerability in patients receiving ripretinib versus sunitinib after treatment with imatinib in INTRIGUE, a phase 3, open-label study1
    (2023) Gelderblom, Hans; Jones, Robin L.; Blay, Jean-Yves; George, Suzanne; von Mehren, Margaret; Zalcberg, John R.; Kang, Yoon-Koo; Razak, Albiruni Abdul; Trent, Jonathan; Attia, Steven; Le Cesne, Axel; Siontis, Brittany L.; Goldstein, David; Boye, Kjetil; Sanchez, Cesar; Steeghs, Neeltje; Rutkowski, Piotr; Druta, Mihaela; Serrano, Cesar; Somaiah, Neeta; Chi, Ping; Harrow, Brooke; Becker, Claus; Reichmann, William; Sherman, Matthew L.; Ruiz-Soto, Rodrigo; Heinrich, Michael C.
    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 & GE;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.& COPY; 2023 Deciphera Pharmaceuticals LLC. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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    Ripretinib versus sunitinib in gastrointestinal stromal tumor: ctDNA biomarker analysis of the phase 3 INTRIGUE trial
    (2024) Heinrich, Michael C.; Jones, Robin L.; George, Suzanne; Gelderblom, Hans; Schoeffski, Patrick; von Mehren, Margaret; Zalcberg, John R.; Kang, Yoon-Koo; Razak, Albiruni Abdul; Trent, Jonathan; Attia, Steven; Le Cesne, Axel; Siontis, Brittany L.; Goldstein, David; Boye, Kjetil; Sanchez, Cesar; Steeghs, Neeltje; Rutkowski, Piotr; Druta, Mihaela; Serrano, Cesar; Somaiah, Neeta; Chi, Ping; Reichmann, William; Sprott, Kam; Achour, Haroun; Sherman, Matthew L.; Ruiz-Soto, Rodrigo; Blay, Jean-Yves; Bauer, Sebastian
    INTRIGUE was an open-label, phase 3 study in adult patients with advanced gastrointestinal stromal tumor who had disease progression on or intolerance to imatinib and who were randomized to once-daily ripretinib 150 mg or sunitinib 50 mg. In the primary analysis, progression-free survival (PFS) with ripretinib was not superior to sunitinib. In clinical and nonclinical studies, ripretinib and sunitinib have demonstrated differential activity based on the exon location of KIT mutations. Therefore, we hypothesized that mutational analysis using circulating tumor DNA (ctDNA) might provide further insight. In this exploratory analysis (N = 362), baseline peripheral whole blood was analyzed by a 74-gene ctDNA next-generation sequencing-based assay. ctDNA was detected in 280/362 (77%) samples with KIT mutations in 213/362 patients (59%). Imatinib-resistant mutations were found in the KIT ATP-binding pocket (exons 13/14) and activation loop (exons 17/18). Mutational subgroup assessment showed 2 mutually exclusive populations with differential treatment effects. Patients with only KIT exon 11 + 13/14 mutations (ripretinib, n = 21; sunitinib, n = 20) had better PFS with sunitinib versus ripretinib (median, 15.0 versus 4.0 months). Patients with only KIT exon 11 + 17/18 mutations (ripretinib, n = 27; sunitinib, n = 25) had better PFS with ripretinib versus sunitinib (median, 14.2 versus 1.5 months). The results of this exploratory analysis suggest ctDNA sequencing may improve the prediction of the efficacy of single-drug therapies and support further evaluation of ripretinib in patients with KIT exon 11 + 17/18 mutations. ClinicalTrials.gov identifier: NCT03673501.