medwireNews: In nonprogressing patients with advanced gastrointestinal stromal tumors (GIST), imatinib interruption leads to worse outcomes and faster emergence of resistance, indicate long-term results from the French BFR14 trial.
“In all treatment guidelines for GIST, it is recommended that imatinib treatment be maintained until progression or intolerance in patients with advanced GIST, but, in routine practice, treatment interruption is often requested by patients,” write the researchers in The Lancet Oncology.
“Given the absence of an effect of treatment interruption on overall survival and resistance to imatinib observed in the first reports of the BFR14 study, flexibility for interruption is occasionally proposed. But the results shown here indicate that imatinib interruption should be considered with caution.”
In the phase 3 open-label trial, patients with unresectable locally advanced or metastatic GIST who had controlled disease (complete or partial response or stable disease) following 1, 3, or 5 years of treatment with imatinib 400 mg/day were randomly assigned to discontinue imatinib with reintroduction at progression (interruption group) or to continue with the tyrosine kinase inhibitor until progression or intolerance (continuation group).
A total of 32 patients were allocated to the interruption group and 26 to the continuation group after 1 year of imatinib, while the corresponding numbers were 25 and 25 after 3 years, and 14 and 13 after 5 years. The respective median follow-up durations for the current analysis were 235.2, 200.9, and 164.5 months.
Jean-Yves Blay (Centre Léon Bérard, Lyon, France) and co-investigators report that progression-free survival was significantly shorter among patients who interrupted rather than continued imatinib after 1, 3, or 5 years, at a median of 6.1 versus 27.8 months, 7.0 versus 67.0 months, 12.0 months versus unreached, respectively. The corresponding hazard ratios for progression or death were 0.36, 0.15, and 0.13 in favor of the continuation approach.
Median overall survival was also significantly shorter with the interruption than continuation strategy for patients who were assigned after 3 years of treatment, at 104 and 134 months, respectively, but not among those assigned after 1 or 5 years of therapy.
“One can speculate that the absence of difference between the interruption and continuation groups at 5 years might be due to a shorter follow-up, the small size of the cohort, or both,” write Blay and colleagues.
They also evaluated time to imatinib resistance, finding no significant difference between the interruption and continuation groups after 1 year of imatinib (28.7 vs 90.6 months), but the median time was significantly shorter with the interruption strategy after 3 and 5 years, at 66.2 versus 127.3 months and 58.6 months versus unreached, respectively.
In light of these findings, the researchers conclude that “[i]matinib interruption in patients with GIST without progressive disease is not recommended.”
The authors of a linked commentary say that “[t]his long-term follow-up from a randomised trial confirms the practice of continuous suppression of the oncogenic driver in advanced GIST.”
Ryan Denu and Neeta Somaiah – both from the University of Texas MD Anderson Cancer Center in Houston, USA – ask whether there are “select patients in whom interruption might be considered.”
They continue: “Learning more about the initial disease characteristics and mutations might shed light on select patients who stay progression free beyond 5 years from discontinuation. Future technology that could reliably detect residual tumour in the blood might be a potential tool to identify and track such patients.”
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