TY - JOUR
T1 - S0502
T2 - A SWOG phase III randomized study of imatinib, with or without bevacizumab, in patients with untreated metastatic or unresectable gastrointestinal stromal tumors
AU - Blanke, Charles D.
AU - Rankin, Cathy
AU - Corless, Christopher
AU - Eary, Janet F.
AU - Mulder, Karen
AU - Okuno, Scott H.
AU - George, Suzanne
AU - Heinrich, Michael
N1 - Publisher Copyright:
© AlphaMed Press 2015.
PY - 2015/11/17
Y1 - 2015/11/17
N2 - Background. Imatinib mesylate, a potent inhibitor of the KIT and PDGFR tyrosine kinases, is highly effective in the treatment of advanced gastrointestinal stromal tumors (GISTs). However, most imatinib-treated tumors eventually become resistant, accounting foramedianprogression-freesurvivalof19–23months.Expression of vascular endothelial growth factor (VEGF) correlates with poor prognosis in GIST; bevacizumab, a monoclonal antibody against VEGF, is effective in a variety of solid tumors. We postulated combination therapy with imatinib plus bevacizumab would benefit patients with advanced GIST, particularly those reliant on VEGFA-dependent angiogenesis. Methods. PatientswithmetastaticorsurgicallyunresectableGIST were eligible for this phase III open-label clinical trial, S0502. At registration, patients were randomly assigned to either imatinib 400mg(standard)or 800mg(patientswith exon 9 KITmutations), or imatinib plus bevacizumab, 7.5 mg/kg i.v. every 3 weeks. Patients were treated to progression, symptomatic deterioration, unacceptable toxicity, treatment delay greater than 4 weeks, or patient choice towithdraw fromthe study.The primary objective was to determine whether the addition of bevacizumab to imatinib would improve progression-free survival (PFS) in first-line treatment of incurable GIST. Results. S0502 opened on April 15, 2008. As of fall 2009, only 12 patients from at least 178 eligible SWOG centers plus those participating through Cancer Trials Support Unit had been entered in the study. Despite an aggressive promotion scheme involving the other cooperative groups and a major GIST patient advocacy group, accrual remained slow. The trial was closed on October 1, 2009, having accrued only 2% of the 572 patients planned. No scientific conclusionswere forthcoming because of the small number of patients entered in the study. Two patients of the 6 in the combination arm reported grade 3 toxicities, 1 with proteinuria and 1 with fatigue, upper gastrointestinal hemorrhage, and anemia. Conclusion. No conclusions may be drawn from this trial and, thus, the combination of imatinib plus bevacizumab cannot be recommended for use.
AB - Background. Imatinib mesylate, a potent inhibitor of the KIT and PDGFR tyrosine kinases, is highly effective in the treatment of advanced gastrointestinal stromal tumors (GISTs). However, most imatinib-treated tumors eventually become resistant, accounting foramedianprogression-freesurvivalof19–23months.Expression of vascular endothelial growth factor (VEGF) correlates with poor prognosis in GIST; bevacizumab, a monoclonal antibody against VEGF, is effective in a variety of solid tumors. We postulated combination therapy with imatinib plus bevacizumab would benefit patients with advanced GIST, particularly those reliant on VEGFA-dependent angiogenesis. Methods. PatientswithmetastaticorsurgicallyunresectableGIST were eligible for this phase III open-label clinical trial, S0502. At registration, patients were randomly assigned to either imatinib 400mg(standard)or 800mg(patientswith exon 9 KITmutations), or imatinib plus bevacizumab, 7.5 mg/kg i.v. every 3 weeks. Patients were treated to progression, symptomatic deterioration, unacceptable toxicity, treatment delay greater than 4 weeks, or patient choice towithdraw fromthe study.The primary objective was to determine whether the addition of bevacizumab to imatinib would improve progression-free survival (PFS) in first-line treatment of incurable GIST. Results. S0502 opened on April 15, 2008. As of fall 2009, only 12 patients from at least 178 eligible SWOG centers plus those participating through Cancer Trials Support Unit had been entered in the study. Despite an aggressive promotion scheme involving the other cooperative groups and a major GIST patient advocacy group, accrual remained slow. The trial was closed on October 1, 2009, having accrued only 2% of the 572 patients planned. No scientific conclusionswere forthcoming because of the small number of patients entered in the study. Two patients of the 6 in the combination arm reported grade 3 toxicities, 1 with proteinuria and 1 with fatigue, upper gastrointestinal hemorrhage, and anemia. Conclusion. No conclusions may be drawn from this trial and, thus, the combination of imatinib plus bevacizumab cannot be recommended for use.
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U2 - 10.1634/theoncologist.2015-0295
DO - 10.1634/theoncologist.2015-0295
M3 - Article
C2 - 26576593
AN - SCOPUS:84949943036
SN - 1083-7159
VL - 20
SP - 1353
EP - 1354
JO - Oncologist
JF - Oncologist
IS - 12
ER -