Primary GIST Recurrence Halted During 5-Year Imatinib Therapy

Gastrointestinal stromal tumours did not recur during a 5-year course of adjuvant imatinib despite around half of patients discontinuing treatment

medwireNews: The PERSIST-5 investigators say none of the patients treated for primary gastrointestinal stromal tumours (GISTs) that were sensitive to imatinib developed recurrent disease during their 5-year course of adjuvant treatment with the tyrosine kinase inhibitor. 

“A randomized trial of 3-year therapy vs 5-year therapy of imatinib that is currently under way will help determine whether a longer duration of therapy is superior”, say Chandrajit Raut, from Brigham and Women’s Hospital in Boston, Massachusetts, USA, and co-workers. 

The current phase II trial included 91 adults who underwent macroscopically complete surgery for GIST expressing KIT with an intermediate or high risk of recurrence, based on their GIST size, location and/or mitotic count. 

The patients were all assigned to receive oral imatinib 400 mg/day for 5 years or until disease progression or intolerance, but the median treatment duration was just 55.1 months, with only 51% of patients completing the full course of treatment.  

The estimated 5-year recurrence-free survival rate was 90% and overall survival was 95%, the investigators report in JAMA Oncology

One patient developed disease recurrence during imatinib therapy and subsequently died; this individual was found to have a PDGFRA exon 18 D842V mutation that is associated with lack of sensitivity to imatinib. 

A further three patients developed recurrence after choosing to end treatment early, two patients had recurrence after discontinuing imatinib because of adverse events, and one patient developed recurrence after completing the planned regime. 

Of note, five of these six patients tested positive for the PDGFRA exon 18 D842V mutation or another genetic marker for imatinib insensitivity, the researchers observe. 

Quality of life scores were “stable” among the 40 patients who completed treatment. But the team admits that as patients who discontinued therapy did not complete the QoL surveys, “no associations between QoL and early discontinuation could be made.” 

Chandrajit Raut and colleagues say the lack of QoL data from earlier imatinib trials makes it “difficult to know what could have been done to reduce this dropout rate.” 

Hypothesising that clinician support might help to improve patient adherence to treatment, they add: “Although this is a relatively well-tolerated drug with proven survival efficacy in the adjuvant setting, retaining patients on therapy after a curative operation is challenging.” 



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