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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

  • Bone and Soft Tissue Sarcomas
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 07 March 2012

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.

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Acknowledgment

Supported in part by grants RTOG U10 CA21661 and CCOP U10 CA37422 from the National Cancer Institute (NCI). The contents of this article are the sole responsibility of the authors and do not necessarily represent the official views of the NCI. The authors received consulting fees, honoraria, and research support as follows: Consulting: Charles D. Blanke (Novartis), George D. Demetri (Novartis), Margaret von Mehren (Novartis), Burt Eisenberg (Novartis), Michael Heinrich (Novartis, MolecularMD). Honoraria: Charles D. Blanke (Novartis), George D. Demetri (Novartis), Michael Heinrich (Novartis), Margaret. von Mehren (Novartis), Burt Eisenberg (Novartis). Research support: George D. Demetri (Novartis), Margaret. von Mehren (Novartis). Michael Heinrich (Novartis, Ariad, Lilly, AROG Pharmaceuticals), Scott Okuno (Novartis). Stock ownership: Michael Heinrich (MolecularMD).

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Authors and Affiliations

  1. Medical College of Wisconsin, Milwaukee, WI, USA

    Dian Wang MD, PhD

  2. Radiation Therapy Oncology Group Statistical Center, Philadelphia, PA, USA

    Qiang Zhang PhD

  3. University of British Columbia and British Columbia Cancer Agency, Vancouver, BC, Canada

    Charles D. Blanke MD

  4. Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA

    George D. Demetri MD

  5. Portland VA Medical Center and Oregon Health & Science University, Portland, OR, USA

    Michael C. Heinrich MD

  6. Fox Chase Cancer Center, Philadelphia, PA, USA

    James C. Watson MD, John P. Hoffman MD & Margaret von Mehren MD

  7. Mayo Clinic, Rochester, MN, USA

    Scott Okuno MD

  8. Roswell Park Cancer Institute, Buffalo, NY, USA

    John M. Kane MD

  9. Dartmouth-Hitchcock Medical Center, Lebanon, NH

    Burton L. Eisenberg MD

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  1. Dian Wang MD, PhD
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  2. Qiang Zhang PhD
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  3. Charles D. Blanke MD
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  4. George D. Demetri MD
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  10. Margaret von Mehren MD
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  11. Burton L. Eisenberg MD
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Corresponding author

Correspondence to Dian Wang MD, PhD.

Additional information

An erratum to this article can be found at http://dx.doi.org/10.1245/s10434-012-2228-3.

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Wang, D., Zhang, Q., Blanke, C.D. et al. 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. Ann Surg Oncol 19, 1074–1080 (2012). https://doi.org/10.1245/s10434-011-2190-5

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  • DOI: https://doi.org/10.1245/s10434-011-2190-5

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