Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial
- Abstract
- Background: PDGFRA D842V mutations occur in 5-10% of gastrointestinal stromal tumours (GISTs), and previously approved tyrosine kinase inhibitors (TKIs) are inactive against this mutation. Consequently, patients have a poor prognosis. We present an updated analysis of avapritinib efficacy and long-term safety in this patient population.
Methods: NAVIGATOR (NCT02508532), a two-part, open-label, dose-escalation/dose-expansion phase I study, enrolled adult patients with unresectable GISTs. Patients with PDGFRA D842V-mutant GIST were a prespecified subgroup within the overall safety population, which included patients who received ≥1 avapritinib dose. Primary end-points were overall response rate (ORR) and avapritinib safety profile. Secondary end-points were clinical benefit rate (CBR), duration of response (DOR) and progression-free survival (PFS). Overall survival (OS) was an exploratory end-point.
Results: Between 7 October 2015 and 9 March 2020, 250 patients enrolled in the safety population; 56 patients were included in the PDGFRA D842V population, 11 were TKI-naive. At data cut-off, median follow-up was 27.5 months. Safety profile was comparable between the overall safety and PDGFRA D842V populations. In the PDGFRA D842V population, the most frequent adverse events were nausea (38 [68%] patients) and diarrhoea (37 [66%]), and cognitive effects occurred in 32 (57%) patients. The ORR was 91% (51/56 patients). The CBR was 98% (55/56 patients). The median DOR was 27.6 months (95% confidence interval [CI]: 17.6-not reached [NR]); median PFS was 34.0 months (95% CI: 22.9-NR). Median OS was not reached.
Conclusion: Targeting PDGFRA D842V-mutant GIST with avapritinib resulted in an unprecedented, durable clinical benefit, with a manageable safety profile. Avapritinib should be considered as first-line therapy for these patients.
- Author(s)
- 강윤구; Ce´sar Serrano; Ferry A.L.M. Eskens; Margaret von Mehren; Maria Roche; Michael C. Heinrich; Olivier Mir; Patrick Scho¨ffski; Philippe A. Cassier; Piotr Rutkowski; Robin L. Jones; Sant P. Chawla; Sebastian Bauer; Suzanne George; Teresa Zhou; William D. Tap
- Issued Date
- 2021
- Type
- Article
- Keyword
- Analysis; Avapritinib; Clinical trials; Gastrointestinal stromal tumours; Medical; Experimental; Metastasis; PDGFRA; Phase 1; Platelet-derived growth factor; Product development; Tyrosine
- DOI
- 10.1016/j.ejca.2020.12.008
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/8399
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_proquest_miscellaneous_2479418261&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Avapritinib%20in%20unresectable%20or%20metastatic%20PDGFRA%20D842V-mutant%20gastrointestinal%20stromal%20tumours:%20Long-term%20efficacy%20and%20safety%20data%20from%20the%20NAVIGATOR%20phase%20I%20trial&offset=0&pcAvailability=true
- Publisher
- EUROPEAN JOURNAL OF CANCER
- Location
- 영국
- Language
- 영어
- ISSN
- 0959-8049
- Citation Volume
- 145
- Citation Number
- 0
- Citation Start Page
- 132
- Citation End Page
- 142
-
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