Nilotinib Inferior to Imatinib in First-Line Treatment of Unresectable or Metastatic GIST


Key Points

  • Nilotinib was associated with poorer progression-free survival in patients with unresectable or metastatic GIST.
  • Trial accrual was stopped early due to futility.

In the phase III ENESTg1 trial reported in The Lancet Oncology, Blay et al found that nilotinib (Tasigna) was associated with poorer progression-free survival vs imatinib (Gleevec) as first-line treatment in patients with unresectable or metastatic gastrointestinal stromal tumors (GIST). Trial accrual was terminated early due to futility on interim analysis.

In this open-label trial, 647 patients were randomly assigned between March 2009 and April 2011, when accrual was terminated, to receive nilotinib at 400 mg twice daily  (n = 324) or imatinib at 400 mg once daily (n = 320). The primary endpoint was progression-free survival.

Poorer Progression-Free and Overall Survival

The interim futility analysis included 397 evaluable patients and showed significantly greater risk of progression in the nilotinib group (24% vs 14%, hazard ratio [HR] = 2.03, 95% confidence interval [CI] = 1.27–3.24).

In the final analysis of the full population, 24-month progression-free survival was 51.6% in the nilotinib group vs 59.2% in the imatinib group (HR = 1.47, 95% CI = 1.10–1.95), and 24-month overall survival was 81.8% vs 90.0% (HR = 1.85, 95% CI = 1.20–2.86).

Adverse Events

The most common grade 3 or 4 adverse events were anemia (6%), elevated lipase (5%), elevated ALT (4%), and abdominal pain (3%) in the nilotinib group and hypophosphatemia (6%), anemia (5%), abdominal pain (4%), and elevated lipase (5%) in the imatinib group.

The investigators concluded: “Nilotinib cannot be recommended for broad use to treat first-line GIST. However, future studies might identify patient subsets for whom first-line nilotinib could be of clinical benefit.”

Jean-Yves Blay, MD, of University Claude Bernard Lyon I, is the corresponding author for the Lancet Oncology article.

The study was funded by Novartis Pharmaceuticals. For full disclosures of the study authors, visit

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