This research aimed to compare the relative efficacy of avapritinib versus midostaurin for patients with advanced systemic mastocytosis. A systematic literature review was performed to identify relevant evidence. Unanchored matching-adjusted indirect comparisons were conducted for overall survival (OS), overall response rate (ORR) and complete remission (CR). The systematic literature review identified the clinical trials EXPLORER and PATHFINDER (investigating avapritinib) and D2201 and A2213 (investigating midostaurin). The avapritinib versus midostaurin adjusted hazard ratio for OS was 0.44 (95% CI: 0.25-0.76), and the adjusted odds ratios for ORR and CR were 4.06 (95% CI: 3.09-5.33) and 9.56 (95% CI: 0.97-93.81), respectively. The results suggest that avapritinib improves survival and response (ORR and CR) compared with midostaurin.
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http://dx.doi.org/10.2217/fon-2021-1509 | DOI Listing |
NEJM Evid
June 2023
Institute of Allergology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin.
BACKGROUND: Indolent systemic mastocytosis (ISM) is a clonal mast-cell disease driven by the KIT D816V mutation. We assessed the efficacy and safety of avapritinib versus placebo, both with best supportive care, in patients with ISM. METHODS: We randomized patients with moderate to severe ISM (total symptom score [TSS] of ≥28; scores range from 0 to 110, with higher numbers indicating more severe symptoms) two to one to avapritinib 25 mg once daily (n=141) or placebo (n=71).
View Article and Find Full Text PDFClin Cancer Res
February 2024
Department of Gastrointestinal Oncology, Laboratory of Carcinogenesis and Translational Research of the Ministry of Education, Peking University School of Oncology, Beijing Cancer Hospital & Institute, Beijing, China.
Purpose: The efficacy of the selective KIT/PDGFRA inhibitor avapritinib (300 mg once daily) was explored in patients with non-PDGFRA-mutant gastrointestinal stromal tumors (GISTs) from the phase I NAVIGATOR and phase I/II CS3007-001 trials.
Patients And Methods: Adults with unresectable/metastatic, KIT-only-mutant GISTs and progression following ≥1 tyrosine kinase inhibitors (TKIs) were included in this post hoc analysis. Baseline mutational status was identified in tumor and plasma.
Ann Oncol
July 2023
Department of Medical Oncology, Sarcoma Center, Dana-Farber Cancer Institute, Boston, USA.
Background: The current treatment paradigm of imatinib-resistant metastatic gastrointestinal stromal tumor (GIST) does not incorporate KIT/PDGFRA genotypes in therapeutic drug sequencing, except for PDGFRA exon 18-mutant GIST that is indicated for avapritinib treatment. Here, circulating tumor DNA (ctDNA) sequencing was used to analyze plasma samples prospectively collected in the phase III VOYAGER trial to understand how the KIT/PDGFRA mutational landscape contributes to tyrosine kinase inhibitor (TKI) resistance and to determine its clinical validity and utility.
Patients And Methods: VOYAGER (N = 476) compared avapritinib with regorafenib in patients with KIT/PDGFRA-mutant GIST previously treated with imatinib and one or two additional TKIs (NCT03465722).
Leukemia
August 2022
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Advanced systemic mastocytosis (AdvSM) is a rare myeloid neoplasm associated with poor overall survival (OS). This study (NCT04695431) compared clinical outcomes between patients with AdvSM treated with avapritinib in the Phase 1 EXPLORER (NCT0256198) and Phase 2 PATHFINDER (NCT03580655) trials (N = 176) and patients treated with best available therapy (BAT; N = 141). A multi-center, observational, retrospective chart review study was conducted at six study sites (four European, two American) to collect data from patients with AdvSM who received BAT; these data were pooled with data from EXPLORER and PATHFINDER.
View Article and Find Full Text PDFFuture Oncol
April 2022
Blueprint Medicines, Zug, 6300, Switzerland.
This research aimed to compare the relative efficacy of avapritinib versus midostaurin for patients with advanced systemic mastocytosis. A systematic literature review was performed to identify relevant evidence. Unanchored matching-adjusted indirect comparisons were conducted for overall survival (OS), overall response rate (ORR) and complete remission (CR).
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