Outcome of patients with Platelet Derived Growth Factor Receptor Alpha-mutated GIST in the tyrosine kinase inhibitor era
Mené sur 58 patients atteints d'une tumeur stromale gastro-intestinale avancée présentant des mutations du gène PDGFRA, cette étude internationale évalue l'efficacité de l'imatinib en fonction des types de mutation (durée de suivi : 46 mois)
Purpose:PDGFRA mutations are found in approximately 5-7% of advanced GIST. We sought to extensively assess the activity of imatinib (IM) in this subgroup. Experimental Design:We conducted an international survey among GIST referral centers to collect clinical data on patients with advanced PDGFRA mutant GISTs treated with IM for advanced disease. Results:: Fifty-eight patients were included, 34 were male (59%), median age at treatment initiation was 61 (range 19-83) years. The primary tumor was gastric in 40 cases (69%). Thirty-two patients (55%) had PDGFRA-D842V substitutions while 17 (29%) had mutations affecting other codons of exon 18, and 9 patients (16%) had mutation in other exons. Fifty seven patients were evaluable for response, 2 (4%) had a complete response, 8 (14%) had a partial response, and 23 (40%) had stable disease. None of 31 evaluable patients with D842V substitution had a response, while 21/31 (68%) had progression as their best response. Median progression-free survival was 2.8 (95%CI: 2.6-3.2) months for patients with D842V substitution and 28.5 months (95% CI: 5.4- 51.6 months) for patients with other PDGFRA mutations. With 46 months of follow-up, median overall survival was 14.7 months for patients with D842V substitutions and was not reached for patients with non-D842V mutations. Conclusions:This study is the largest reported to date on patients with advanced PDGFRA mutant GIST treated with IM. Our data confirm that IM has little efficacy in the subgroup of patients with D842V substitution in exon 18, while other mutations appear to be sensitive to IM.