Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation and predicts outcome in patients with mucosal melanoma

Katherine Zukotynski, Jeffrey T Yap, Anita Giobbie-Hurder, Jeffrey Weber, Rene Gonzalez, Thomas F Gajewski, Steven O'Day, Kevin Kim, F Stephen Hodi, Annick D Van den Abbeele, Katherine Zukotynski, Jeffrey T Yap, Anita Giobbie-Hurder, Jeffrey Weber, Rene Gonzalez, Thomas F Gajewski, Steven O'Day, Kevin Kim, F Stephen Hodi, Annick D Van den Abbeele

Abstract

Background: In patients with metastatic melanoma and KIT amplifications and/or mutations, therapy with imatinib mesylate may prolong survival. 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT may be used to assess metabolic response. We investigated associations of metabolic response, mutational status, progression-free survival and overall survival in this population.

Methods: Baseline and 4-week follow-up 18F-FDG-PET/CT were evaluated in 17 patients with metastatic melanoma and KIT amplifications and/or mutations treated with imatinib in a multicenter phase II clinical trial. The maximum standardized uptake values (SUVmax) were measured in up to 10 lesions on each scan. Metabolic response was classified using modified EORTC criteria. Each patient had a diagnostic CT or MR at baseline, after 6 weeks of therapy and then at intervals of 2 months and anatomic response was classified using RECIST 1.0. Median follow-up was 9.8 months.

Results: Partial metabolic response (PMR), stable metabolic disease (SMD) and progressive metabolic disease (PMD) was seen in 5 (29%), 5 (29%), and 7 (41%) patients respectively. Five patients (29%) had a KIT mutation in exon 11, four of whom (80%) had PMR while 1 (20%) had SMD. Twelve patients (71%) did not have a KIT mutation in exon 11, and only 1 (8%) had PMR, 4 (33%) had SMD and 7 (58%) had PMD. There was agreement of metabolic and anatomic classification in 12 of 17 patients (71%). Four of 17 patients (24%) had PR on both metabolic and anatomic imaging and all had a KIT mutation in exon 11. Survival of patients with PMD was lower than with SMD or PMR.

Conclusions: Metabolic response by 18F-FDG-PET/CT is associated with mutational status in metastatic melanoma patients treated with imatinib. 18F-FDG-PET/CT may be a predictor of outcome, although a larger study is needed to verify this.

Clinical trial registration: NCT00424515.

Figures

Figure 1
Figure 1
Waterfall plots of metabolic response by lesion (a) and patient (b). Three subjects were classified as PMD based on the presence of new lesions rather than % change SUVmax & have not been included in the waterfall plot above.
Figure 2
Figure 2
Representative18F-FDG-PET/CT images showing progression in a patient without an exon 11 KIT mutation (a-d) and response in a patient with an exon 11 KIT mutation (e-h) at baseline (a-b, e-f) and after 1 month of therapy (c-d, g-h). Red arrows point to sites of disease. Reprinted with permission. © (2013) American Society of Clinical Oncology. All rights reserved. From: Hodi S, et al. J Clin Oncol. 31(26), 2013:3182-3190.
Figure 3
Figure 3
Time-to-progression (a) and overall survival (b) by metabolic response (Met).

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