Risk of relapse with imatinib (IM) discontinuation at 5 years in advanced GIST patients: Results of the prospective BFR14 randomized phase III study comparing interruption versus continuation of IM at 5 years of treatment: A French Sarcoma Group Study.

Abstract

10032 Background: We previously showed in the BFR14 study that IM interruption results in increased risk of disease progression (PD) after 1 and 3 years (yr) in non progressing patients (pts). The impact of IM discontinuation on progression free survival (PFS) in responding pts at 5 yrs is unknown. Methods: This prospective multicenter BFR14 study was initiated in 06/02 and completed inclusion in 05/09. After 1, 3, and 5 yrs of IM 400 mg/day, pts free from PD were randomly offered to continue (C arm) or Stop (S arm) IM. Pts allocated to the S arm had to restart IM (same dose) in case of PD. Primary endpoint was PFS. A Bayesian model was implemented for this part of the BFR14 study. Results: Overall, 434 pts were included in the BFR14 study. Fifty-eight (n=26 vs. n=32), 50 (n=25 vs. n=25) and 21 (n=11 vs. n=10) non progressive pts at were randomized at 1, 3 or 5 yrs in the S vs C arms. The 2 yr-PFS were 13% and 16% in the S arms after 1 and 3 years of treatment compared to 62% and 80% in the C arms after 1 and 3 yrs of IM respectively. 21 pts responding to IM at 5 yrs and not previously randomized in the 1 or 3 yrs S arms were randomized after 5 yrs of IM. After a median follow-up of 12 months (6.8-15.1) from randomization, 5 of the 11 pts randomized in the S arm have relapsed while no relapse was observed among the 10 pts randomized in the C arm (p=0.035) The results compare favorably to the 1 yr and 3 yrs cohort for the C arms: 1 year after randomization at 1, 3, and 5 years, the relapse rate was 20% in the 1 yr C cohort, vs. 8% in the 3 yrs C cohort, vs. 0% in the 5-yrs C cohort. IM reintroduction in the I arm (at 1, 3 or 5 yrs) after a reprogression allowed a tumor control in all evaluable pts to date. Conclusions: Despite long term tumor control, IM interruption at 5 yrs resulted in a higher rate of progression than imatinib maintenance in patients with advanced GIST in this randomized study. IM has to be given continuously until PD or intolerance in the population of non progressing advanced or metastatic GIST. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer, GlaxoSmithKline, Novartis, Pfizer, PharmaMar, Roche, sanofi-aventis Chugai Pharma, GlaxoSmithKline, Novartis, Novo Nordisk, Pfizer, PharmaMar, Roche Merck, Novartis, Pfizer, Roche Novartis, PharmaMar