First-Line Nilotinib Not Recommended for Unresectable, Metastatic GISTs

Neither progression-free nor overall survival is improved in patients with gastrointestinal stromal tumours given first-line nilotinib compared with those given imatinib

medwireNews: Compared with imatinib , survival outcomes are not improved with nilotinib treatment in patients with previously untreated unresectable or metastatic gastrointestinal stromal tumours (GISTs), shows the final analysis of a head-to-head trial comparing the two agents.

Indeed, trial accrual was terminated prematurely after the futility boundary was crossed during a planned interim analysis, with results favouring imatinib, the researchers say in The Lancet Oncology.

At 24 months, the progression-free survival (PFS) rate was significantly lower in the 324 participants randomly assigned to receive the second-generation tyrosine kinase inhibitor nilotinib than in the 320 imatinib-treated patients, at 51.6% versus 59.2%.

Patients given nilotinib also fared poorly in terms of overall survival (OS) at 24 months, with a rate of 81.8% in the nilotinib arm and 90.0% in the imatinib one, which was again a significant difference.

And mortality was higher in nilotinib-treated patients than in those given imatinib, with 56 and 32 deaths recorded in either treatment arm, respectively.

When GIST mutation subtypes were taken into consideration, PFS remained poorer with nilotinib treatment than with imatinib for participants with wild-type tumours and those with KIT exon 9 mutations.

But the proportion of patients with KIT exon 11 mutations who achieved PFS was “roughly similar” in both treatment groups, say Jean-Yves Blay, from Centre Léon-Bérard in Lyon, France, and co-authors, cautioning, however, that these results could be biased in favour of nilotinib as a result of “informative censoring”, especially after the interim analysis.

They conclude: “Based on the results of this trial, nilotinib cannot be recommended for the first-line treatment of patients with advanced GIST, but future studies might be able to identify specific subsets of patients who could benefit from this treatment.”

In a linked commentary, Xavier Garcia del Muro, from Institut Català d’Oncologia in Barcelona, Spain, commends the study authors on their “bold” approach, but says that the conclusions leave “no doubt” that “at present, imatinib should be the first-line treatment for patients with advanced GIST, irrespective of the genotype they harbour”.

“Consequently, the only option available today to enhance first-line therapeutic results in everyday medical practice is to optimise imatinib treatment”, he writes, and suggests monitoring plasma imatinib levels in poor responders and improving adherence as potential methods to optimise therapy.

Nonetheless, he believes that despite the negative findings, nilotinib should not be “discarded from the treatment of GIST”, adding: “The potential of nilotinib in specific populations should be explored in greater depth.”


Blay J-Y, Shen L, Kang Y-K, et al. Nilotinib versus imatinib as first-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumours (ENESTg1): a randomised phase 3 trial.Lancet Oncol 2015; Advance online publication 13 April. doi:10.1016/S1470-2045(15)70105-1

del Muro XG. Nilotinib, imatinib, and GIST therapy. Lancet Oncol 2015; Advance online publication 13 April. doi:10.1016/S1470-2045(15)70179-8

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