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

Dian Wang, Qiang Zhang, Charles Blanke, George D. Demetri, Michael Heinrich, James C. Watson, John P. Hoffman, Scott Okuno, John M. Kane, Margaret Von Mehren, Burton L. Eisenberg

    Research output: Contribution to journalArticle

    100 Citations (Scopus)

    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.

    Original languageEnglish (US)
    Pages (from-to)1074-1080
    Number of pages7
    JournalAnnals of Surgical Oncology
    Volume19
    Issue number4
    DOIs
    StatePublished - Apr 2012

    Fingerprint

    Radiation Oncology
    Gastrointestinal Stromal Tumors
    Radiotherapy
    Disease-Free Survival
    Survival
    Maintenance
    Imatinib Mesylate
    Protein-Tyrosine Kinases
    Disease Progression
    Therapeutics

    ASJC Scopus subject areas

    • Surgery
    • Oncology

    Cite this

    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. / Wang, Dian; Zhang, Qiang; Blanke, Charles; Demetri, George D.; Heinrich, Michael; Watson, James C.; Hoffman, John P.; Okuno, Scott; Kane, John M.; Von Mehren, Margaret; Eisenberg, Burton L.

    In: Annals of Surgical Oncology, Vol. 19, No. 4, 04.2012, p. 1074-1080.

    Research output: Contribution to journalArticle

    Wang, Dian ; Zhang, Qiang ; Blanke, Charles ; Demetri, George D. ; Heinrich, Michael ; Watson, James C. ; Hoffman, John P. ; Okuno, Scott ; Kane, John M. ; Von Mehren, Margaret ; Eisenberg, Burton L. / 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. In: Annals of Surgical Oncology. 2012 ; Vol. 19, No. 4. pp. 1074-1080.
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    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.",
    author = "Dian Wang and Qiang Zhang and Charles Blanke and Demetri, {George D.} and Michael Heinrich and Watson, {James C.} and Hoffman, {John P.} and Scott Okuno and Kane, {John M.} and {Von Mehren}, Margaret and Eisenberg, {Burton L.}",
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    T1 - Phase II trial of neoadjuvant/adjuvant imatinib mesylate for advanced primary and metastatic/recurrent operable gastrointestinal stromal tumors

    T2 - Long-term follow-up results of radiation therapy oncology group 0132

    AU - Wang, Dian

    AU - Zhang, Qiang

    AU - Blanke, Charles

    AU - Demetri, George D.

    AU - Heinrich, Michael

    AU - Watson, James C.

    AU - Hoffman, John P.

    AU - Okuno, Scott

    AU - Kane, John M.

    AU - Von Mehren, Margaret

    AU - Eisenberg, Burton L.

    PY - 2012/4

    Y1 - 2012/4

    N2 - 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.

    AB - 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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