Positive long-Term Imatinib Findings For Advanced GIST Patients

Progression-free survival and overall survival results over 10 years of survival are reported for gastrointestinal stromal tumor patients with locally advanced or metastatic disease

medwireNews: Ten-year trial results for imatinib in patients with locally advanced or metastatic gastrointestinal stromal tumours (GISTs) estimate that around a fifth of patients survive but highlight the scarcity of prognostic factors in this population.

The study, which compared the standard 400 mg/day dose of the tyrosine kinase inhibitor with an 800 mg/day regimen in 946 patients from 13 countries, is reported in the Journal of Clinical Oncology. Patients on the lower dose were allowed to cross over to the 800 mg/day dose on progression.

After a median of 10.9 years of follow-up, the median progression-free survival (PFS) in the 400 mg/day and 800 mg/day treatment groups were a comparable 1.7 and 2.0 years, respectively, with a median overall survival (OS) of 3.9 years in both groups.

Kaplan Meier analysis gave estimated 10-year PFS rates of 9.5% and 9.2% for patients in the 400 mg/day and 800 mg/day arms, respectively, with corresponding OS rates of 19.4% and 21.5%, report Paolo Casali, from Istituto Nazionale Tumori in Milan, Italy, and co-authors.

The likelihood of surviving for over 10 years was significantly associated with age below 60 years, a performance status of 0 versus 1 or above, smaller lesion size and a positive test for the exon 11 KIT  mutation versus carriage of the exon 9 mutation or wild-type KIT.

The researchers emphasize that their trial findings are from “the beginning of the learning curve” for imatinib and that participants had “inherently unfavourable prognostic factors”, including a larger than average tumour burden compared with patients with advanced GIST who would begin treatment now.

In addition, GISTs are rare and had only been recently defined before the trial began, Paolo Casali et al write.

“All of these factors add to the value of these long-term results, which basically confirm the sharp improvement in PFS and OS that occurred in the past 15 years for patients with metastatic GIST”, they say, suggesting there may be a potentially better prognosis for patients beginning imatinib now.

Noting that resistance is the major limiting factor for molecular-based therapy, however, the researchers believe that “the presence of a distinct, albeit limited, subset of long-term survivors, and even progression-free survivors, is of high interest clinically and biologically.”

They comment: “It is still to be determined whether a subset of patients with metastatic GIST are liable to be cured by a highly active molecularly targeted agent such as imatinib”, adding that genotype appears to be the only predictive factor for imatinib response and burden the only prognostic marker for duration of response.

“In other words, it is still to be determined whether the presence of a subgroup of long-term progression-free survivors is just the expression of the stochastic mechanisms of tumor resistance, being the tail of a random Gaussian distribution, or is the product of distinct features”, the authors conclude.

Reference

Casali PG, Zalcberg J, Le Cesne A, et al. Ten-year progression-free and overall survival in patients with unresectable or metastatic GI stromal tumors: Long-term analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group and Australasian Gastrointestinal Trials Group Intergroup phase III randomized trial on imatinib at two dose levels. J Clin Oncol; Advance online publication 31 March 2017. DOI: 10.1200/JCO.2016.71.0228

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