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Ripretinib intrapatient dose escalation after disease progression provides clinically meaningful outcomes in advanced gastrointestinal stromal tumour
- Source :
- Eur J Cancer, European Journal of Cancer, 155, 236-244. ELSEVIER SCI LTD
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Purpose: Ripretinib is a switch-control tyrosine kinase inhibitor that broadly inhibits KIT and platelet-derived growth factor receptor a kinase signalling. Ripretinib showed preliminary efficacy in patients with advanced gastrointestinal stromal tumour (GIST) in a phase I study across a range of doses. Results were confirmed in the phase III INVICTUS study, and ripretinib 150 mg once daily (QD) was subsequently approved as a >fourth-line therapy. Here, we report the phase I study results of intrapatient dose escalation (IPDE) in patients with GIST treated across second, third and later lines of therapy. Methods: Patients with advanced GIST who experienced disease progression (PD) at ripretinib 150 mg QD could dose escalate to 150 mg twice daily (BID). Progression-free survival (PFS) 1 was calculated from the date of the first dose of ripretinib 150 mg QD to PD (as per Response Evaluation Criteria in Solid Tumours 1.1); PFS2 was from the date of IPDE (150 mg BID) to PD or death. Treatment-emergent adverse events (TEAEs) were summarised by dosing periods and compared descriptively. Results: Of 142 patients with GIST receiving ripretinib 150 mg QD, 67 underwent IPDE. IPDE provided benefit across all lines of therapy; the median PFS2 was 5.6, 3.3 and 4.6 months for patients on second-, third-and >fourth-line therapy, respectively. A partial metabolic response after IPDE was demonstrated in 13 of 37 patients with available positron emission tomography scans. TEAEs reported at both doses were similar. Conclusion: Ripretinib IPDE after PD provided continued clinical benefit in advanced GIST across second, third and later lines of therapy with a similar safety profile to that observed with the QD regimen. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
- Subjects :
- Male
Oncology
Cancer Research
medicine.medical_specialty
Stromal cell
Gastrointestinal Stromal Tumors
medicine.drug_class
Ripretinib
Article
Tyrosine-kinase inhibitor
Internal medicine
medicine
Humans
Urea
Dosing
Progression-free survival
Naphthyridines
Adverse effect
Protein Kinase Inhibitors
Pharmacology
Gastrointestinal stromal tumours
medicine.diagnostic_test
GiST
business.industry
Progression-Free Survival
Regimen
Treatment Outcome
Positron emission tomography
Disease Progression
Female
business
Subjects
Details
- ISSN :
- 09598049
- Volume :
- 155
- Database :
- OpenAIRE
- Journal :
- European Journal of Cancer
- Accession number :
- edsair.doi.dedup.....dd1083de587e22696969bfa7e860b616