Two-year adjuvant imatinib mesylate after complete resection of localized, high-risk GIST with KIT exon 11 mutation

Cancer Chemother Pharmacol. 2013 Jan;71(1):43-51. doi: 10.1007/s00280-012-1970-3. Epub 2012 Oct 7.

Abstract

Purpose: To evaluate the efficacy and safety of 2-year adjuvant imatinib for patients at high risk of recurrence after complete resection of localized gastrointestinal stromal tumor with KIT exon 11 mutation.

Methods: Imatinib 400 mg/d was administered until disease recurrence, intolerable toxicities, or for 2 years. The primary end point was recurrence-free survival.

Results: Patients (n = 47) from 4 centers in Korea were enrolled. Treatment was well tolerated. Grade 3-4 toxicities included neutropenia (27.7%), skin rash (8.5%), anorexia (4.3%), and constipation (2.1%). At a median follow-up of 56.7 months, 19 patients had recurrences. Median recurrence-free survival was 58.9 months, which was significantly longer than 22.7 months from historical data of 27 patients in the pre-imatinib era (P < 0.0001). Imatinib was rechallenged for 15 patients with recurrence after completion of adjuvant imatinib. Thirteen patients had partial response, and two had stable disease. There was only one death so far.

Conclusions: Postoperative adjuvant imatinib for 2 years was safe and could prolong the recurrence-free survival in patients with a high risk of recurrence after complete resection of localized KIT exon 11 mutated gastrointestinal stromal tumor. Reintroduction of imatinib after recurrence appears to be effective if the recurrence develops after completion of adjuvant imatinib.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Chemotherapy, Adjuvant / methods
  • Disease-Free Survival
  • Exons
  • Female
  • Follow-Up Studies
  • Gastrointestinal Neoplasms / drug therapy*
  • Gastrointestinal Neoplasms / genetics
  • Gastrointestinal Neoplasms / surgery
  • Gastrointestinal Stromal Tumors / drug therapy*
  • Gastrointestinal Stromal Tumors / genetics
  • Gastrointestinal Stromal Tumors / surgery
  • Humans
  • Imatinib Mesylate
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Recurrence, Local
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Prospective Studies
  • Proto-Oncogene Proteins c-kit / genetics*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Republic of Korea
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Proto-Oncogene Proteins c-kit