Advanced GIST Mutations May Alter Regorafenib Response

Regorafenib efficacy may be linked to metastatic or unresectable gastrointestinal stromal tumour mutation presence

medwireNews: Tumour genotyping may help predict response to regorafenib in patients with metastatic or inoperable gastrointestinal stromal tumour (GIST) for whom tyrosine kinase inhibitor (TKI) therapy has failed, suggest extended follow-up results from a phase II trial of the oral multi-kinase inhibitor.

After a median of 41 months of follow-up, 25 of the 33 patients who received regorafenib 160 mg/day on 21 days of a 28-day cycle experienced a clinical benefit, defined as a complete or partial response or stable disease lasting at least 16 weeks.

This included six patients who achieved a partial response, report Suzanne George, from Dana Farber Cancer Institute in Boston, Massachusetts, USA, and co-workers in the Annals of Oncology.

Median progression-free survival was 13.2 months and was significantly longer in the 15 patients whose GIST had an activating KIT exon 11 mutation than the two patients without succinate dehydrogenase (SDH)-deficient tumour mutations (ie, wild-type genotypes for KIT and PDGFRA), at a median of 13.4 versus 1.6 months.

The six patients with SDH-deficient GIST had a median PFS of 10.0 months, falling to 5.7 months for the two patients with an exon 9 KIT mutation.

Of note, four patients remained free from progression when the study was closed, with a PFS of between 36.8 and 43.5 months; two of these patients had SDH-deficient mutant tumours, one patient had an exon 11 KIT mutation and the remaining patient had an exon 9 KIT mutation.

Median overall survival was 25.0 months but did not significantly differ between the patient genotype groups, the investigators say.

“Increased activity of regorafenib in specific refractory GIST molecular subtypes warrants further investigation”, they believe.

The long-term safety profile of regorafenib was “consistent with previous reports”, the authors say, with any-grade hand–foot skin reactions (91%), fatigue (85%), diarrhoea (79%) and hypertension (76%) common.

At least one grade 3–4 event was reported for 31 of the patients, and the majority of participants required at least one delay in treatment (56%), a dose withheld (88%), or a dose reduction because of protocol-defined toxicity (82%).

Nevertheless, the researchers say that “drug discontinuation was rare, and a small subset of patients remained on regorafenib treatment for more than 3 years.” 

Reference

Ben-Ami E, Barysauskas CM, von Mehren M, et al. Long-term follow-up results of the multicenter phase II trial of regorafenib in patients with metastatic and/or unresectable GI stromal tumor after failure of standard tyrosine kinase inhibitor therapy. Ann Oncol 2016; Advance online publication 1 July. doi: 10.1093/annonc/mdw228

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2016