An imaging study of vemurafenib in patients with BRAFV600-mutated metastatic melanoma.

Abstract

e19034 Background: Targeted therapy against the mutated form of BRAF V600 is a proven effective therapy for melanoma. Objective of this exploratory study was to describe the change over time of PET-scan results and verify the association of PET-scan examination with the objective response (OR) (defined by RECIST criteria) in melanoma pts treated with vemurafenib. These preliminary results reported here regards the description of changes over time of PET-scan. Methods: Patients treated with vemurafenib at our institution were considered eligible. Patients were evaluated with PET-scan at baseline and at day 7, 15 and 30 from the start of therapy. Maximal Standardized Uptake Value (SUVmax) and Total Lesion Glycolysis (mean SUV x lesion volume) were recorded and compared for single lesions in the 4 exams. Differences between each PET-scan performed during therapy and baseline were calculated and coded as yes/no response basing on predefined criteria. Association of PET responses and achievement of OR were estimated by means of logistic regression models. Odds ratio and C statistics were used to define strength of association and discriminant capability. C statistics obtained with PET/CT at different timepoints were compared. Results: As of January 2012, 7 out of 20 required pts have been enrolled. A total of 48 lesions were available for evaluation. A reduction in lesion SUVmax and TLG values compared to baseline was evident in all the post-therapy studies (reduction in SUV max at day 7 – 51 ± 28 %, day 14 – 67 ± 24 % and day 30 –69 ± 29 %, reduction in TLG at day 7 – 41 ± 83 %, day 14 – 69 ± 35 % and day 30 – 68 ± 37 %). A comparison of the day 15 and day 30 studies showed essentially stable uptake values (SUV max variation -3 ± 41 %, TLG 5 ± 56 %). However, 14/23 lesions in 3 patients showed increased SUV max and TLG values between the day 15 and day 30 studies likely indicating early signs of treatment resistance. Conclusions: Our preliminary results suggest that PET/CT may be an early surrogate marker of treatment response to vemurafenib. Sequential monitoring of targeted therapy with PET/CT may be useful in identification of treatment resistance, aid in tailoring alternative strategies and deserves further investigation.