TY - JOUR
T1 - Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era
AU - Cassier, Philippe A.
AU - Fumagalli, Elena
AU - Rutkowski, Piotr
AU - Schöffski, Patrick
AU - Van Glabbeke, Martine
AU - Debiec-Rychter, Maria
AU - Emile, Jean François
AU - Duffaud, Florence
AU - Martin-Broto, Javier
AU - Landi, Bruno
AU - Adenis, Antoine
AU - Bertucci, François
AU - Bompas, Emmanuelle
AU - Bouché, Olivier
AU - Leyvraz, Serge
AU - Judson, Ian
AU - Verweij, Jaap
AU - Casali, Paolo
AU - Blay, Jean Yves
AU - Hohenberger, Peter
PY - 2012/8/15
Y1 - 2012/8/15
N2 - Purpose: Platelet-derived growth factor receptor-alpha (PDGFRA) mutations are found in approximately 5%to7%of advanced gastrointestinal stromal tumors (GIST). Wesought to extensively assess the activity of imatinib 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 imatinib for advanced disease. Results: Fifty-eight patients were included, 34 were male (59%), and 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 whereas 17 (29%) had mutations affecting other codons of exon 18, and nine patients (16%) had mutation in other exons. Fifty-seven patients were evaluable for response, two (4%) had a complete response, eight (14%) had a partial response, and 23 (40%) had stable disease. None of 31 evaluable patients with D842V substitution had a response, whereas 21 of 31 (68%) had progression as their best response. Median progression-free survival was 2.8 [95% confidence interval (CI), 2.6-3.2] months for patients with D842V substitution and 28.5 months (95% CI, 5.4-51.6) 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 GISTs treated with imatinib. Our data confirm that imatinib has little efficacy in the subgroup of patients with D842V substitution in exon 18, whereas other mutations appear to be sensitive to imatinib.
AB - Purpose: Platelet-derived growth factor receptor-alpha (PDGFRA) mutations are found in approximately 5%to7%of advanced gastrointestinal stromal tumors (GIST). Wesought to extensively assess the activity of imatinib 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 imatinib for advanced disease. Results: Fifty-eight patients were included, 34 were male (59%), and 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 whereas 17 (29%) had mutations affecting other codons of exon 18, and nine patients (16%) had mutation in other exons. Fifty-seven patients were evaluable for response, two (4%) had a complete response, eight (14%) had a partial response, and 23 (40%) had stable disease. None of 31 evaluable patients with D842V substitution had a response, whereas 21 of 31 (68%) had progression as their best response. Median progression-free survival was 2.8 [95% confidence interval (CI), 2.6-3.2] months for patients with D842V substitution and 28.5 months (95% CI, 5.4-51.6) 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 GISTs treated with imatinib. Our data confirm that imatinib has little efficacy in the subgroup of patients with D842V substitution in exon 18, whereas other mutations appear to be sensitive to imatinib.
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U2 - 10.1158/1078-0432.CCR-11-3025
DO - 10.1158/1078-0432.CCR-11-3025
M3 - Article
C2 - 22718859
AN - SCOPUS:84865100068
VL - 18
SP - 4458
EP - 4464
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 16
ER -