Imatinib and GISTs: Genomic Subtypes and Survival Outcomes

Some unresectable gastrointestinal stromal tumors (GISTs) with KIT and PDGFRA mutations respond to imatinib therapy and may extend a patient’s overall survival by as much as a decade, according to an article published in JAMA Oncology.¹

Chemotherapy is notoriously ineffective for patients with a metastatic or unresectable GIST; it was shown, however, that GISTs with a KIT exon 11 mutation respond to imatinib through a proof-of-concept study and several phase 2 and 3 trials. This randomized phase 3 study (ClinicalTrials.gov Identifier: NCT00009906) was designed to determine whether 400 mg or 800 mg is the optimal dose in this setting.

Of 695 enrolled patients with surgically-incurable cancer, 346 were randomized to receive the standard 400-mg imatinib dose and 349 received an 800-mg dose. After 8 years, 95 patients in the 400-mg dose group and 94 patients in the 800-mg dose group were alive, indicating no difference in overall survival between the cohorts. Nearly half of all surviving patients received imatinib only.

Of 395 genotype analyses for particular patients, 282 harbored KIT exon 11 mutations, 32 had KIT exon 9 mutations, 67 “had the KIT/PDGFRA WT genotype,” and 14 had other KIT/PDGFRA mutations. Patients with KIT exon 11 mutations had a median overall survival of 66 months, over 2 years longer than for any other genotype.

Adverse events were not discussed.

The authors concluded that imatinib markedly improves overall survival for patients with GISTs harboring KIT and PDGFRA mutations, particularly for those with an exon 11 mutation. Further research is needed for other GIST subtypes.

Reference

1. Heinrich M, Rankin C, Blanke CD, et al. Correlation of long-term results of imatinib in advanced gastrointestinal stromal tumors with next-generation sequencing results: analysis of phase 3 SWOG Intergroup Trial S0033. JAMA Oncol. 2017 Feb 9. doi: 10.1001/jamaoncol.2016.6728 [Epub ahead of print]