Early prediction of response to sunitinib after imatinib failure by 18F-Fluorodeoxyglucose Positron emission tomography in patients with gastrointestinal stromal tumor

John O. Prior, Michael Montemurro, Maria Victoria Orcurto, Olivier Michielin, François Luthi, Jean Benhattar, Louis Guillou, Valérie Elsig, Roger Stupp, Angelika Bischof Delaloye, Serge Leyvraz

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Abstract

Purpose Positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure. Patients and Methods Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Results Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P <.0001). Using - 25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P<.0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P <.0001), primary resistance to imatinib (P =.024), or nongastric GIST (P =.002), regardless of the mutational status of the KIT and PDGFRA genes. Conclusion Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.

Original languageEnglish (US)
Pages (from-to)439-445
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number3
DOIs
StatePublished - Jan 20 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Prior, J. O., Montemurro, M., Orcurto, M. V., Michielin, O., Luthi, F., Benhattar, J., Guillou, L., Elsig, V., Stupp, R., Delaloye, A. B., & Leyvraz, S. (2009). Early prediction of response to sunitinib after imatinib failure by 18F-Fluorodeoxyglucose Positron emission tomography in patients with gastrointestinal stromal tumor. Journal of Clinical Oncology, 27(3), 439-445. https://doi.org/10.1200/JCO.2008.17.2742