Originally published as JCO Early Release 10.1200/JCO.2008.17.2742 on December 8 2008

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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

From the Nuclear Medicine, Pathology, and Medical Oncology Departments, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland

Corresponding author: John O. Prior, MD, PhD, Rue du Bugnon 46, Lausanne, Switzerland CH-1011; e-mail: John.Prior{at}chuv.ch

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.

published online ahead of print at www.jco.org on December 8, 2008.

Supported in part by Pfizer Inc, New York, NY within the frame of two clinical studies (A6181004 and A6181036); and by the Nuclear Medicine Department, Center Hospitalier Universitaire Vaudois, Lausanne, Switzerland. J.O.P., MD, PhD, was recipient of an Academic Research Award from the Leenaards Foundation (Lausanne, Switzerland).

Presented in part at the 7th Annual Meeting of the Swiss Society of Nuclear Medicine, June 1-3, 2006, Lausanne, Switzerland; and at the 53rd Annual Meeting of the Society of Nuclear Medicine, June 3-7, 2006, San Diego, CA.

The study was performed within the frame of two identical clinical protocols registered at ClinicalTrial.gov under identifiers NCT00075218 [ClinicalTrials.gov] and NCT00094029 [ClinicalTrials.gov] .

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Clinical trial information can be found for the following: NCT00075218 [ClinicalTrials.gov] , NCT00094029 [ClinicalTrials.gov]

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