Investigational MKIs Improve Outcomes in Metastatic GIST

Using first-line multi-kinase inhibitors (MKIs) besides imatinib did not lead to early resistance or decreased efficacy of second-line treatment in patients with metastatic gastrointestinal stromal tumors (GIST; ESMO Open. 2020;5[6]:e001082).

“Imatinib is the standard first-line therapy in metastatic [GIST],” Alice Boileve, MD, Gustave Roussy, Villejuif, France, and co-investigators wrote.  Researchers noted investigational MKIs such as nilotinib, dasatinib and masitinib have been tested as first-line treatment in phase 2/3 studies and sought to investigate if this could lead to improved survival, or early emergence of resistance to approved MKIs, in second-line treatment.

In order to assess if using the investigational MKIs in first-line therapy decreases imatinib efficacy in second-line for patients with GIST, researchers performed a retrospective chart review from 2005 to 2011in two French tertiary centers, of patients with GIST who received first-line investigational MKIs in phase 2/3 trials followed by second-line imatinib treatment.

A total of 46 patients were included in the retrospective study, of which 55% were women, 47% (n=22) had a KIT exon 11 mutation, 1 patient each had a KIT exon 9 mutation and PDGFRA D842V mutation.

Patients had previously received masitinib(n=21), dasatinib(n=17), or nilotinib(n=8) as first-line treatment and had a median progression-free survival of 18.0 months.

Researchers observed the median time to failure of imatinib was 19.7 months (95%CI: 13.5 to 29.0); and median time to second relapse was 48.7 months. From the time of metastatic diagnosis, the median overall survival was 5.7 years.

“Patients with GIST who received investigational MKIs as first-line treatment and imatinib as second line had a time to second relapse longer than that observed historically with imatinib in first line, suggesting that using MKIs other than imatinib in first line does not decrease the efficacy of subsequent treatment lines,” researchers concluded.—Kaitlyn Manasterski