Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2013 Sep;258(3):422-9.
doi: 10.1097/SLA.0b013e3182a15eb7.

Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial

Ronald P DeMatteo  1 , Karla V Ballman, Cristina R Antonescu, Christopher Corless, Violetta Kolesnikova, Margaret von Mehren, Martin D McCarter, Jeffrey Norton, Robert G Maki, Peter W T Pisters, George D Demetri, Murray F Brennan, Kouros Owzar; American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team for the Alliance for Clinical Trials in Oncology
Affiliations
Clinical Trial

Long-term results of adjuvant imatinib mesylate in localized, high-risk, primary gastrointestinal stromal tumor: ACOSOG Z9000 (Alliance) intergroup phase 2 trial

Ronald P DeMatteo et al. Ann Surg. 2013 Sep.

Abstract

Objective: To conduct the first adjuvant trial of imatinib mesylate for treatment of gastrointestinal stromal tumor (GIST).

Background: GIST is the most common sarcoma. Although surgical resection has been the mainstay of therapy for localized, primary GIST, postoperative tumor recurrence is common. The KIT protooncogene or, less frequently, platelet-derived growth factor receptor alpha is mutated in GIST; the gene products of both are inhibited by imatinib mesylate.

Methods: This was a phase II, intergroup trial led by the American College of Surgeons Oncology Group, registered at ClinicalTrials.gov as NCT00025246. From September 2001 to September 2003, we accrued 106 patients who had undergone complete gross tumor removal but were deemed at high risk for recurrence. Patients were prescribed imatinib 400 mg per day for 1 year and followed with serial radiologic evaluation. The primary endpoint was overall survival (OS).

Results: After a median follow-up of 7.7 years, the 1-, 3-, and 5-year OS rates were 99%, 97%, and 83%, which compared favorably with a historical 5-year OS rate of 35%. The 1-, 3-, and 5-year recurrence-free survival (RFS) rates were 96%, 60%, and 40%. On univariable analysis, age and mitotic rate were associated with OS. On multivariable analysis, the RFS rate was lower with increasing tumor size, small bowel site, KIT exon 9 mutation, high mitotic rate, and older age.

Conclusions: Adjuvant imatinib in patients with primary GIST who are at high risk of recurrence prolongs OS compared with that of historical controls. Optimal duration of adjuvant therapy remains undefined. (NCT00025246).

PubMed Disclaimer

Figures

Figure 1
Figure 1
CONSORT diagram.
Figure 2
Figure 2
Recurrence-free survival. Figure 2A. Entire population. Figure 2B. Mutation status.
Figure 2
Figure 2
Recurrence-free survival. Figure 2A. Entire population. Figure 2B. Mutation status.
Figure 3
Figure 3
Overall survival. Figure 3A. Entire population. Figure 3B. Mutation status.
Figure 3
Figure 3
Overall survival. Figure 3A. Entire population. Figure 3B. Mutation status.
See this image and copyright information in PMC

References

    1. Ducimetiere F, Lurkin A, Ranchere-Vince D, et al. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One. 2011;6(8):e20294. - PMC - PubMed
    1. Joensuu H, DeMatteo RP. The management of gastrointestinal stromal tumors: A model for targeted and multidisciplinary therapy of malignancy. Annu Rev Med. 2012;63:247–58. - PMC - PubMed
    1. DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. 2000 Jan;231(1):51–8. - PMC - PubMed
    1. DeMatteo RP, Heinrich MC, El-Rifai WM, et al. Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol. 2002 May;33(5):466–77. - PubMed
    1. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998 Jan 23;279(5350):577–80. - PubMed

Publication types

MeSH terms

Associated data