Influence of imatinib interruption and rechallenge on the residual disease in patients with advanced GIST: results of the BFR14 prospective French Sarcoma Group randomised, phase III trial

Ann Oncol. 2013 Apr;24(4):1087-93. doi: 10.1093/annonc/mds587. Epub 2012 Nov 21.

Abstract

Background: We previously demonstrated that interruption of imatinib mesylate (IM) in responding patients (pts) with advanced gastrointestinal stromal tumours (GISTs) results in rapid reprogression. The impact of interruption on residual tumour, quality of response and secondary resistance has not been fully investigated.

Patients and methods: Within the BRF14 study, 71 non-progressing patients were randomly assigned in the interruption arms after 1, 3 or 5 years. IM was resumed in the case of progressive disease (PD). Tumour status at randomisation, relapse and after IM rechallenge, progression-free survival (PFS) and time to secondary resistance were analysed.

Results: At data cut-off, 51 of 71 patients had restarted IM following documented PD. Eighteen patients (35%) progressed on known lesions only, while 33 patients (65%) had new lesions, with concomitant progression of known lesions in 17 patients. Only 8 (42%) of complete remission (CR) patients and 12 (52%) of partial response (PR) patients at randomisation achieved a new CR and PR. Patients progressing rapidly after interruption had a poorer prognosis. Tumour status at randomisation influenced time to progression after rechallenge.

Conclusion: In advanced GIST patients interrupting IM, quality of response upon reintroduction did not reach the tumour status observed at randomisation. Rapid progression after imatinib interruption is associated with poor PFS after reintroduction.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzamides / administration & dosage*
  • Benzamides / adverse effects
  • Disease Progression
  • Disease-Free Survival
  • Drug Administration Schedule*
  • Female
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Piperazines / administration & dosage*
  • Piperazines / adverse effects
  • Prospective Studies
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Treatment Outcome

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate