Interruption of Imatinib Therapy after 5 Years Increases Risk of
Relapse in Patients with Advanced GIST
Patients with advanced gastrointestinal stromal tumors (GIST)
treated with imatinib must continue to receive therapy continuously
until disease progression or intolerance. These long-term data from
the BFR14 French Sarcoma Group study confirmed earlier similar
findings noted after 1 and 3 years postrandomization. These results
were originally presented at the 2010 ASCO Annual Meeting by
Isabelle Ray-Coquard, MD, PhD, of the Centre Léon Bérard, Lyon,
France. Suzanne George, MD, Clinical Director,
Center for Sarcoma and Bone Oncology, Dana-Farber Cancer Institute,
and Assistant Professor in Medicine, Harvard Medical School,
summarized these findings at the Best of ASCO Meeting in
Boston.1
Earlier Analysis Confirmed
BFR14 was a prospective, randomized phase III
trial comparing interruption and continuation of imatinib therapy
in patients with advanced or metastatic GIST. Patients (N = 434)
who responded or had stable disease with imatinib, after remaining
on imatinib for 1, 3, or 5 years, were randomly assigned to cohorts
that either continued imatinib or halted therapy (Fig. 1). Those
who stopped drug treatment could resume imatinib upon disease
progression. The trial started in 2002 and completed enrollment in
2009.
Previous analyses after interruptions at 1 and 3 years had
demonstrated that progression-free survival (PFS), the primary
endpoint, was significantly longer at both time points in the
groups that continued to receive therapy.2 For example,
in patients who were randomly assigned after 3 years, those who
continued imatinib therapy had a 2-year PFS rate of 80%, compared
to 16% in those who stopped treatment (log-rank P <
.0001). In the 5-year cohort, 25 patients with stable disease were
randomly assigned to either the continued-therapy group or the
treatment-interruption group.
The most recent update of BFR14,
which randomly assigned patients with metastatic GIST who had been
stable on 5 years of imatinib, again demonstrated very similar
findings. After a median follow-up of 11.9 months
postrandomization, relapse occurred in 7 of 13 patients in the
interruption group vs 0 of 12 patients in the continued-therapy
group (P = .032). For those who continued imatinib
therapy, the relapse rate at 5 years was superior to the rates at 1
and 3 years (0% vs 20% and 8%, respectively). ■
References
1. Ray-Coquard I, Bin Bui N, Adenis A, et al: 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. Best of ASCO Boston. Abstract 10032. Presented July 23, 2010, by
Suzanne George, MD.
2. Blay JY, Adenis A, Ray-Coquard I, et al: Is there a role for
discontinuing imatinib in patients with advanced gastrointestinal
stromal tumour? Curr Opin Oncol 21:360-366, 2009.
