In a long-term follow-up of a French phase III trial (BFR14) reported in The Lancet Oncology, Jean-Yves Blay, MD, and colleagues found that discontinuation of imatinib in patients with advanced gastrointestinal stromal tumors (GIST) with at least stable disease was associated with markedly poorer progression-free survival vs continuation of imatinib.
Jean-Yves Blay, MD
Study Details
In the multicenter trial, patients received imatinib at 400 mg daily. Those with a complete or partial response or stable disease at 1, 3, and 5 years from the start of treatment were randomly assigned to imatinib discontinuation until disease progression (interruption group) or imatinib continuation until disease progression (continuation group).
Key Findings
Randomization to the interruption group vs the continuation group included 32 vs 26 patients after 1 year of imatinib, 25 vs 25 patients after 3 years of imatinib, and 14 vs 13 patients after 5 years of imatinib. Median follow-up was 235.2 months after the 1-year randomization, 200.9 months after the 3-year randomization, and 164.5 months after the 5-year randomization.
Median progression-free survival data in the interruption group vs the continuation group were:
- 6.1 months (95% confidence interval [CI] = 2.5–10.1 months) vs 27.8 months (95% CI = 19.5–37.9 months) after 1 year of imatinib (hazard ratio [HR] = 0.36, 95% CI = 0.20–0.64, P = .0003)
- 7.0 months (95% CI = 3.5–11.7 months) vs 67.0 months (95% CI = 48.8–85.6 months) after 3 years of imatinib (HR = 0.15, 95% CI = 0.07–0.32, P < .0001)
- 12.0 months (95% CI = 9.0–16.6 months) vs not reached (95% CI = not reached to not reached) after 5 years of imatinib (HR = 0.13, 95% CI = 0.03–0.58, P = .0016).
Data on the median time to imatinib resistance in the interruption group vs the continuation group were:
- 28.7 months vs 90.6 months after 1 year of imatinib (HR = 0.93, 95% CI = 0.51–1.71, P = .82)
- 66.2 months vs 127.3 months after 3 years of imatinib (HR = 0.35, 95% CI = 0.17–0.72, P = .0028)
- 58.6 months vs not reached after 5 years of imatinib (HR = 0.24, 95% CI = 0.05–1.12, P = .049).
Median overall survival data in the interruption group vs the continuation group were:
- 56.0 months (95% CI = 30.3–82.9 months) vs 105.0 months (95% CI = 20.6–189.6 months) after 1 year of imatinib (HR = 0.84, 95% CI = 0.46–1.54, P = .57)
- 104.0 months (95% CI = 90.7–118.7 months) vs 134.0 months (95% CI = 89.7–178.3 months) after 3 years (HR = 0.40, 95% CI = 0.20–0.82, P = .0096)
- Not reached (95% CI = not reached to not reached) vs 110.4 months (95% CI = 82.7–154.1 months) after 5 years (HR = 1.28, 95% CI = 0.41–3.99, P = .67).
The investigators concluded: “Imatinib interruption in patients with GIST without progressive disease is not recommended. These updated results…. show that the interruption of imatinib after 3 years and 5 years of administration in patients with advanced GIST results not only in rapid re-progression of the disease… but also in faster development of resistance to imatinib in the long term. A shorter overall survival was also observed in patients in the interruption group vs the continuation group at 3 years.”
Dr. Blay, of Centre Léon Bérard, Université Claude Bernard Lyon I and Centre de Recherche en Cancérologie de Lyon, Lyon, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by Centre Léon Bérard, INCa, CONTICANET, Ligue Contre le Cancer, and Novartis. For full disclosures of the study authors, visit thelancet.com.
