Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era.
OBJECTIVE
Platelet-derived growth factor receptor-alpha (PDGFRA) mutations are found in approximately 5% to 7% of advanced gastrointestinal stromal tumors (GIST). We sought to extensively assess the activity of imatinib in this subgroup.


METHODS
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.
Department of Medicine, Centre Léon Bérard, Lyon, France. cassierp@hotmail.com
Philippe A
PA
Cassier
Elena
E
Fumagalli
Piotr
P
Rutkowski
Patrick
P
Schöffski
Martine
M
Van Glabbeke
Maria
M
Debiec-Rychter
Jean-François
JF
Emile
Florence
F
Duffaud
Javier
J
Martin-Broto
Bruno
B
Landi
Antoine
A
Adenis
François
F
Bertucci
Emmanuelle
E
Bompas
Olivier
O
Bouché
Serge
S
Leyvraz
Ian
I
Judson
Jaap
J
Verweij
Paolo
P
Casali
Jean-Yves
JY
Blay
Peter
P
Hohenberger
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D005091:Exons; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D020796:Receptor, Platelet-Derived Growth Factor alpha