dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Jones, Robin L. |
dc.contributor.author | Serrano Garcia, César |
dc.contributor.author | von Mehren, Margaret |
dc.contributor.author | Heinrich, Michael C. |
dc.contributor.author | Kang, Yoon-Koo |
dc.contributor.author | George, Suzanne |
dc.date.accessioned | 2021-07-05T08:27:28Z |
dc.date.available | 2021-07-05T08:27:28Z |
dc.date.issued | 2021-03 |
dc.identifier.citation | Jones RL, Serrano C, von Mehren M, George S, Heinrich MC, Kang YK, et al. Avapritinib in unresectable or metastatic PDGFRA D842V-mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial. Eur J Cancer. 2021 Mar;145:132-142. |
dc.identifier.issn | 0959-8049 |
dc.identifier.uri | https://hdl.handle.net/11351/6119 |
dc.description | Avapritinib; Gastrointestinal stromal tumours; PDGFRA |
dc.description.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-naïve. 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. |
dc.language.iso | eng |
dc.publisher | Elsevier |
dc.relation.ispartofseries | European Journal of Cancer;145 |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.source | Scientia |
dc.subject | Mutació (Biologia) |
dc.subject | Inhibidors enzimàtics - Ús terapèutic - Eficàcia |
dc.subject | Aparell digestiu - Càncer |
dc.subject.mesh | Gastrointestinal Stromal Tumors |
dc.subject.mesh | /drug therapy |
dc.subject.mesh | Mutation |
dc.subject.mesh | Treatment Outcome |
dc.title | Avapritinib in unresectable or metastatic PDGFRA D842V - mutant gastrointestinal stromal tumours: Long-term efficacy and safety data from the NAVIGATOR phase I trial |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1016/j.ejca.2020.12.008 |
dc.subject.decs | tumores del estroma gastrointestinal |
dc.subject.decs | /farmacoterapia |
dc.subject.decs | mutación |
dc.subject.decs | resultado del tratamiento |
dc.relation.publishversion | https://linkinghub.elsevier.com/retrieve/pii/S0959804920314234 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut Català de la Salut |
dc.contributor.authoraffiliation | [Jones RL] Royal Marsden Hospital and Institute of Cancer Research, London, UK. [Serrano C] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain. [von Mehren M] Fox Chase Cancer Center, Philadelphia, PA, USA. [George S] Dana-Farber Cancer Institute, Boston, MA, USA. [Heinrich MC] Portland VA Health Care System and OHSU Knight Cancer Institute, Portland, OR, USA. [Kang YK] Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea |
dc.identifier.pmid | 33465704 |
dc.identifier.wos | 000625301200013 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |