| Abstract: |
Purpose: Imaging with [ 18F]fluorodeoxyglucose (FDG) -positron emission tomography (PET) allows early recognition of a response to agents that target key driver mutations in human cancer. We aimed to determine the metabolic response rate to vemurafenib in patients with advanced BRAF-mutant melanoma. Patients and Methods: Baseline and day 15 FDG-PET was evaluated in 31 patients with advanced melanoma treated in a phase I study of dose escalation of vemurafenib (PLX06-02), which included four patients treated at subtherapeutic doses and 24 patients treated at 960 mg twice a day, which is the maximum-tolerated dose of vemurafenib. Results: All 27 patients treated at potentially therapeutic levels had at least a partial metabolic response, and three patients achieved a complete metabolic response. In the 27 patients, there was an 80% ± 3% reduction in the maximum standardized uptake value (SUVmax) of target lesions and an 87% ± 3% decrease in the percentage of injected dose (%ID) in all identified disease sites. There was a positive correlation between %ID in all identified disease and target-lesion SUVmax (r 2 = 0.66; P < .001) that indicated a significant homogeneity of the response between lesions in individual patients. Although no relationship was found between the reduction in target lesion SUVmax and best response according to RECIST (Response Evaluation Criteria in Solid Tumors), there was a trend for patients with greater reductions in uptake of FDG to have longer progression-free survival. Conclusion: FDG-PET is a useful marker of an early biologic response to vemurafenib. Little variability in PET response was found between lesions in individual patients, which suggested minimal intrapatient molecular heterogeneity. FDG-PET is a useful tool for the evaluation of the biologic impact of inhibiting mutant BRAF and may allow for the more effective development of novel agents. © 2012 by American Society of Clinical Oncology. |
| Keywords: |
survival; adult; clinical article; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; survival analysis; unclassified drug; genetics; mutation; clinical trial; mortality; advanced cancer; dose response; cancer patient; comparative study; cancer staging; positron emission tomography; follow up; methodology; follow-up studies; neoplasm staging; monitoring; metabolism; melanoma; progression free survival; skin neoplasms; drug administration schedule; tumor markers, biological; pathology; dose-response relationship, drug; tumor marker; drug dose escalation; cancer invasion; confidence interval; confidence intervals; skin tumor; correlation analysis; diagnostic agent; early diagnosis; sulfonamide; sulfonamides; fluorodeoxyglucose f 18; fluorodeoxyglucose f18; positron-emission tomography; clinical evaluation; scintiscanning; australia; neoplasm invasiveness; maximum tolerated dose; phase 1 clinical trial; drug administration; indoles; indole derivative; b raf kinase; statistics, nonparametric; proto-oncogene proteins b-raf; braf protein, human; nonparametric test; monitoring, physiologic; vemurafenib; plx 06 02
|
