Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors: long-term follow-up results of Radiation Therapy Oncology Group 0132.

Abstract

BACKGROUND:

Imatinib inhibits the KIT and PDGFR tyrosine kinases, resulting in its notable antitumor activity in gastrointestinal stromal tumor (GIST). We previously reported the early results of a multi-institutional prospective trial (RTOG 0132) using neoadjuvant/adjuvant imatinib either in primary resectable GIST or as a planned preoperative cytoreduction agent for metastatic/recurrent GIST. METHODS.: Patients with primary GIST (≥5 cm, group A) or resectable metastatic/recurrent GIST (≥2 cm, group B) received neoadjuvant imatinib (600 mg/day) for approximately 2 months and maintenance postoperative imatinib for 2 years. We have now updated the clinical outcomes including progression-free survival, disease-specific survival, and overall survival at a median follow-up of 5.1 years, and we correlate these end points with duration of imatinib therapy.

RESULTS:

Sixty-three patients were originally entered (53 analyzable: 31 in group A and 22 in group B). Estimated 5-year progression-free survival and overall survival were 57% in group A, 30% in group B; and 77% in group A, 68% in group B, respectively. Median time to progression has not been reached for group A and was 4.4 years for group B. In group A, in 7 of 11 patients, disease progressed >2 years from registration; 6 of 7 patients with progression had stopped imatinib before progression. In group B, disease progressed in 10 of 13 patients>2 years from registration; 6 of 10 patients with progressing disease had stopped imatinib before progression. There was no significant increase in toxicity compared with our previous short-term analysis.

CONCLUSIONS:

This long-term analysis suggests a high percentage of patients experienced disease progression after discontinuation of 2-year maintenance imatinib therapy after surgery. Consideration should be given to studying longer treatment durations in intermediate- to high-risk GIST patients.

• Authors: Dian Wang, Qiang Zhang, Charles D Blanke, George D Demetri, Michael C Heinrich, James C Watson, John P Hoffman, Scott Okuno, John M Kane, Margaret von Mehren, Burton L Eisenberg
• Journal: Annals of surgical oncology (Ann Surg Oncol) Vol. 19 Issue 4 Pg. 1074-80 (Apr 2012) ISSN: 1534-4681 [Electronic] United States
• PMID: 22203182 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)

Chemical References

• Benzamides
• Piperazines
• Protein Kinase Inhibitors
• Pyrimidines
• Imatinib Mesylate

Topics

• Adult
• Aged
• Aged, 80 and over
• Benzamides
• Chemotherapy, Adjuvant
• Disease Progression
• Disease-Free Survival
• Female
• Follow-Up Studies
• Gastrointestinal Stromal Tumors (drug therapy, mortality, secondary)
• Humans
• Imatinib Mesylate
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Piperazines (adverse effects, therapeutic use)
• Protein Kinase Inhibitors (adverse effects, therapeutic use)
• Pyrimidines (adverse effects, therapeutic use)
• Survival Rate
• Treatment Outcome
• Young Adult