Imatinib interruption linked to poorer outcomes in advanced gastrointestinal stromal tumors
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Key takeaways:
- Imatinib interruption resulted in shorter median OS.
- Interruption also appeared linked to rapid progression and shorter time to imatinib resistance.
Imatinib interruption should not be considered for patients with advanced gastrointestinal stromal tumor who do not have progressive disease, according to results of a randomized phase 3 trial.
Patients assigned imatinib interruption had shorter OS and more rapid disease progression. They also developed resistance to imatinib more quickly.
Limited data exists regarding the long-term effect of tyrosine kinase inhibitor discontinuation on resistance and survival among patients with advanced gastrointestinal stromal tumors (GIST).
Researchers conducted the randomized phase 3 BFR14 trial to assess long-term outcomes of patients who experienced an imatinib interruption during treatment.
The open-label trial included adults with advanced GIST treated at one of 17 comprehensive cancer centers or hospitals in France. All participants had ECOG performance status of 0 to 3 and had received no prior imatinib.
Patients received 400 mg oral imatinib daily. Those who achieved complete or partial response or who exhibited stable disease at 1 year, 3 years or 5 years from treatment initiation were randomly assigned to either continue imatinib until disease progression or discontinue treatment.
PFS served as the primary endpoint. Secondary endpoints included OS and time to imatinib resistance.
Researchers randomly assigned 58 patients after 1 year of imatinib to treatment interruption (n = 32) or treatment continuation (n = 26).
Investigators randomly assigned 50 patients after 3 years of imatinib to treatment interruption (n = 25) or continuation (n = 25).
They randomly assigned 27 patients who completed 5 years of imatinib treatment to interruption (n = 14) or continuation (n = 13).
Researchers reported median follow-ups of 235.2 months (interquartile range, 128.8-236.6) for those randomly assigned after 1 year of treatment; 200.9 months (interquartile range, 190.2-208.4) for those randomly assigned after 3 years of treatment; and 164.5 months (interquartile range, 134.4-176.4) for those randomly assigned after 5 years of treatment.
Among those randomly assigned after 1 year of imatinib, results showed significantly longer median PFS among those assigned imatinib continuation vs. interruption (27.8 months vs. 6.1 months; HR = 0.36; 95% CI, 0.2-0.64).
The PFS benefit with treatment continuation persisted in analyses of patients randomly assigned after 3 years of imatinib (67 months vs. 7 months; HR = 0.15; 95% CI, 0.07-0.32) and after 5 years of imatinib (not reached vs. 12 months; HR = 0.13; 95% CI, 0.03-0.58).
Results also showed longer median time to resistance with treatment continuation among those randomly assigned at 1 year (90.6 months vs. 28.7 months; HR = 0.93; 95% CI, 0.51-1.71), 3 years (127.3 months vs. 66.2 months; HR = 0.35; 95% CI, 0.17-0.72) and 5 years (not reached vs. 58.6 months; HR = 0.24; 95% CI, 0.05-1.12).
OS results also favored treatment continuation among those randomly assigned after 1 year (median, 105 months vs. 56 months; HR = 0.84; 95% CI. 0.46-1.54) and 3 years (median, 134 months vs. 104 months; HR = 0.4; 95% CI, 0.2-0.82).
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