Durable Imatinib OS Benefits Found For Some Metastatic GIST Patients

A subgroup of patients with metastatic gastrointestinal stromal tumours have achieved long-term survival with imatinib therapy

medwireNews: The S0033 trial demonstrates that patients with specific metastatic gastrointestinal stromal tumour (GIST) genetic markers can achieve long-term survival with the tyrosine kinase inhibitor imatinib.

“Notably, patients with advanced GIST treated with imatinib alone have experienced survival without report of progression for periods that approach and even exceed 1 decade”, report Michael Heinrich, from Portland Veterans Affairs Health Care System in Oregon, USA, and co-authors in JAMA Oncology.

However, the researchers emphasize: “Although this study provides guidance for management of GIST harboring the most common KIT and PDGFRA mutations, optimal management of other genotypic subtypes remains unclear.”

Long-term survival was achieved by 27.5% of 346 patients with advanced GIST that was not surgically curable who were initially given imatinib 400 mg/day and 26.9% of 349 patients who were originally assigned to receive imatinib 400 mg twice daily.

The 10-year overall survival (OS) was estimated to be 23% and the estimated 10-year progression-free survival (PFS) rate was 7%. At the time of analysis 556 of the patients had died after a median of 52 months.

The researchers highlight that imatinib was the sole therapy given to 48.6% of 142 long-term survivors with additional treatment information, while 51.4% were also given treatment such as sunitinib or sorafenib, radiotherapy or surgery.

Multivariate analysis showed that OS was significantly and positively associated with younger age, being female and having a good performance score at baseline, as well as a smaller tumour diameter, a lower white blood cell count and a higher albumin level.

Genotype data available for 395 patients showed that exon 11 mutations in the KIT gene encoding the tyrosine-protein kinase Kit were present in 71.5%, while 17.0% carried the wild-type alleles for KIT and the platelet-derived growth factor receptor α gene (PDGFRA), 8.1% had a KIT exon 9 mutation and 3.5% other KIT or PDGFRA mutations.

After adjusting for confounders, OS was significantly longer for patients with a KIT exon 11 mutation than wild-type patients and KIT exon 9 mutation carriers, at 66 versus 40 and 38 months, respectively.Further analysis of patients with a KIT exon 11 mutation showed that median OS varied within this group from 65 months for those with a deletion and 66 months for those with a point mutation to 73 months for patients with a insertion/duplication type mutation.

Among the 12 patients with succinate dehydrogenase (SDH)-deficient GIST, there were no complete responses to imatinib and only one partial response (8.3%) versus an overall response rate of 65.6% among the 282 patients with a KIT exon 11-mutated tumour, including complete and partial responses in 6.4% and 59.2%, respectively.

Median adjusted OS did not significantly differ between the SDH-deficient and KIT exon 11 mutation groups, at 116 versus 66 months, although the researchers observe that the confidence intervals in the small SDH-deficient population was “quite broad”.

“Given prior reports of cases of indolent behavior of untreated SDH-deficient metastatic GIST, whether imatinib alters the natural history of most cases of KIT/PDGFRA [wild-type] GIST is unclear”, the authors say.

“Further studies are required to better define the role of imatinib therapy in the treatment of this type of GIST.”

Reference

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; Advance online publication 9 February 2017. doi:10.1001/jamaoncol.2016.6728

medwireNews (www.medwireNews.com) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2017