Among patients with gastrointestinal stromal tumors (GISTs), study results highlighting the variability in treatment responses associated with different GIST mutational profiles showed that patients with a KIT-exon-11 mutation tended to respond more favorably to neoadjuvant Gleevec (imatinib), according to findings published in Cancers.
“Our findings indicate that patients with KIT-exon-11 mutations exhibit a higher rate of partial response and more favorable surgical outcomes compared to those with other mutations,” study authors wrote. “In contrast, patients with non-KIT exon 11 mutations and wild-type KIT/PDGFRA GISTs exhibited less favorable responses to [Gleevec], suggesting that in these cases, the transition to surgery should occur earlier if there is insufficient therapeutic response.”
Patients with HIT-exon 11 mutations had a higher partial response rate to Gleevec, with 60.5% responding compared with 33.3% of those without the mutation.
A positive resection margin, R1 or R2, was observed in patients with non-HIT exon 11 mutations at 21.2% (14 patients), and in those with HIT-exon 11 mutations at 5.5% (11 patients). The median duration of neoadjuvant therapy was shorter in patients with non-HIT exon 11 mutations at 5.3 months compared with 8.8 months in those with HIT-exon 11 mutations.
“These results highlight the importance of mutational profiling in guiding treatment decisions and optimizing outcomes for GIST patients undergoing neoadjuvant therapy,” study authors wrote.
Side effects were not included, which, study authors noted, prevents assessment of the potential toxicity profile of neoadjuvant Gleevec in this cohort.
Between 2009 and 2021, 326 patients received neoadjuvant Gleevec and 264 (80.9%) underwent resection. Among them, 74.6% had a KIT exon 11 mutation, 7.3% had other KIT mutations, 3.8% had a PDGFRA D842 mutation, 6.8% had other PDGFRA mutations, 0.7% had an NTRK mutation, 0.4% had an SDH mutation and 6.4% had wild-type GISTs. Patients with KIT-exon 11 mutations typically started with a 400 milligram (mg) dose of Gleevec, while 72% of those with a KIT-exon 9 mutation received an 800 mg dose.
The primary end goal was response rate of neoadjuvant treatment. Secondary outcomes included resection margin status (negative resection margin versus positive resection margin) and the time on neoadjuvant therapy, which reflects the interval from the start of Gleevec to the time of surgery.
“Our findings might have significant implications for clinical practice,” study authors concluded. “Based on the observed treatment responses, it is clear that mutation testing should guide the decision to transition from neoadjuvant therapy to surgery.”
Reference:
“Impact of Mutation Profile on Outcomes of Neoadjuvant Therapy in GIST” by Dr. Mahmoud Mohammadi, et al., cancers.
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